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  • PD-L1 controls cancer pyroptosis
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-17
    María Teresa Blasco; Roger R. Gomis

    Programmed death ligand-1 (PD-L1) is well known for its role as an immune checkpoint regulator, but little is known about its function in other cellular processes. A study now shows that in tumour cells PD-L1 mediates pyroptosis, an inflammatory form of cell death, by activating the expression of Gasdermine C, ultimately leading to tumour necrosis.

    更新日期:2020-09-18
  • Author Correction: AP-1 imprints a reversible transcriptional programme of senescent cells
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-16
    Ricardo Iván Martínez-Zamudio; Pierre-François Roux; José Américo N.L.F. de Freitas; Lucas Robinson; Gregory Doré; Bin Sun; Dimitri Belenki; Maja Milanovic; Utz Herbig; Clemens A. Schmitt; Jesús Gil; Oliver Bischof

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-09-16
  • PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-14
    Junwei Hou; Rongce Zhao; Weiya Xia; Chiung-Wen Chang; Yun You; Jung-Mao Hsu; Lei Nie; Yeh Chen; Yu-Chuan Wang; Chunxiao Liu; Wei-Jan Wang; Yun Wu; Baozhen Ke; Jennifer L. Hsu; Kebin Huang; Zu Ye; Yi Yang; Xianghou Xia; Yintao Li; Chia-Wei Li; Bin Shao; John A. Tainer; Mien-Chie Hung

    Although pyroptosis is critical for macrophages against pathogen infection, its role and mechanism in cancer cells remains unclear. PD-L1 has been detected in the nucleus, with unknown function. Here we show that PD-L1 switches TNFα-induced apoptosis to pyroptosis in cancer cells, resulting in tumour necrosis. Under hypoxia, p-Stat3 physically interacts with PD-L1 and facilitates its nuclear translocation

    更新日期:2020-09-14
  • Nucleated transcriptional condensates amplify gene expression
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-14
    Ming-Tzo Wei; Yi-Che Chang; Shunsuke F. Shimobayashi; Yongdae Shin; Amy R. Strom; Clifford P. Brangwynne

    Membraneless organelles or condensates form through liquid–liquid phase separation1,2,3,4, which is thought to underlie gene transcription through condensation of the large-scale nucleolus5,6,7 or in smaller assemblies known as transcriptional condensates8,9,10,11. Transcriptional condensates have been hypothesized to phase separate at particular genomic loci and locally promote the biomolecular interactions

    更新日期:2020-09-14
  • lncRNA DIGIT and BRD3 protein form phase-separated condensates to regulate endoderm differentiation
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-07
    Kaveh Daneshvar; M. Behfar Ardehali; Isaac A. Klein; Fu-Kai Hsieh; Arcadia J. Kratkiewicz; Amin Mahpour; Sabrina O. L. Cancelliere; Chan Zhou; Brett M. Cook; Wenyang Li; Joshua V. Pondick; Sweta K. Gupta; Sean P. Moran; Richard A. Young; Robert E. Kingston; Alan C. Mullen

    Cooperation between DNA, RNA and protein regulates gene expression and controls differentiation through interactions that connect regions of nucleic acids and protein domains and through the assembly of biomolecular condensates. Here, we report that endoderm differentiation is regulated by the interaction between the long non-coding RNA (lncRNA) DIGIT and the bromodomain and extraterminal domain protein

    更新日期:2020-09-08
  • Cellular and molecular architecture of the intestinal stem cell niche.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-03
    Neil McCarthy,Judith Kraiczy,Ramesh A Shivdasani

    Intestinal stem and progenitor cells replicate and differentiate in distinct compartments, influenced by Wnt, BMP, and other subepithelial cues. The cellular sources of these signals were long obscure because intestinal mesenchyme was insufficiently characterised. In this Review, we discuss how recent mRNA profiles of mouse and human intestinal submucosa, coupled with fine-resolution microscopy and

    更新日期:2020-09-03
  • Synthetic immunomodulation with a CRISPR super-repressor in vivo.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-03
    Farzaneh Moghadam,Ryan LeGraw,Jeremy J Velazquez,Nan Cher Yeo,Chenxi Xu,Jin Park,Alejandro Chavez,Mo R Ebrahimkhani,Samira Kiani

    Transient modulation of the genes involved in immunity, without exerting a permanent change in the DNA code, can be an effective strategy to modulate the course of many inflammatory conditions. CRISPR-Cas9 technology represents a promising platform for achieving this goal. Truncation of guide RNA (gRNA) from the 5′ end enables the application of a nuclease competent Cas9 protein for transcriptional

    更新日期:2020-09-03
  • Igniting the spread of ferroptotic cell death.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-31
    Andrew J Davidson,Will Wood

    Ferroptosis is an iron-dependent mode of cell death driven by lipid peroxidation, capable of explosively propagating through a field of cells. Two studies now explore the mechanisms underlying ferroptotic cell death and its spread, as well as its possible in vivo significance, shedding light on some of the burning questions surrounding ferroptosis.

    更新日期:2020-08-31
  • Shear stress turns on the primary cilium and lipophagy.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-31
    Nuria Martinez-Lopez,Rajat Singh

    While the formation and concentration of urine are better understood, how kidney epithelial cells generate the energy to drive these functions has remained unclear. A study now reveals that shear stress originating from urinary flow is sensed by the primary cilia of cortical epithelial cells and stimulates lipolysis and oxidative metabolism.

    更新日期:2020-08-31
  • Ferroptosis occurs through an osmotic mechanism and propagates independently of cell rupture.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-31
    Michelle Riegman,Liran Sagie,Chen Galed,Tom Levin,Noah Steinberg,Scott J Dixon,Ulrich Wiesner,Michelle S Bradbury,Philipp Niethammer,Assaf Zaritsky,Michael Overholtzer

    Ferroptosis is a regulated form of necrotic cell death that is caused by the accumulation of oxidized phospholipids, leading to membrane damage and cell lysis1,2. Although other types of necrotic death such as pyroptosis and necroptosis are mediated by active mechanisms of execution3,4,5,6, ferroptosis is thought to result from the accumulation of unrepaired cell damage1. Previous studies have suggested

    更新日期:2020-08-31
  • The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-31
    Caterina Miceli,Federica Roccio,Lucille Penalva-Mousset,Martine Burtin,Christine Leroy,Ivan Nemazanyy,Nicolas Kuperwasser,Marco Pontoglio,Gérard Friedlander,Etienne Morel,Fabiola Terzi,Patrice Codogno,Nicolas Dupont

    Organs and cells must adapt to shear stress induced by biological fluids, but how fluid flow contributes to the execution of specific cell programs is poorly understood. Here we show that shear stress favours mitochondrial biogenesis and metabolic reprogramming to ensure energy production and cellular adaptation in kidney epithelial cells. Shear stress stimulates lipophagy, contributing to the production

    更新日期:2020-08-31
  • Lipid peroxidation regulates long-range wound detection through 5-lipoxygenase in zebrafish.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-31
    Anushka Katikaneni,Mark Jelcic,Gary F Gerlach,Yanan Ma,Michael Overholtzer,Philipp Niethammer

    Rapid wound detection by distant leukocytes is essential for antimicrobial defence and post-infection survival1. The reactive oxygen species hydrogen peroxide and the polyunsaturated fatty acid arachidonic acid are among the earliest known mediators of this process2,3,4. It is unknown whether or how these highly conserved cues collaborate to achieve wound detection over distances of several hundreds

    更新日期:2020-08-31
  • Publisher Correction: Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-27
    Huilin Huang,Hengyou Weng,Wenju Sun,Xi Qin,Hailing Shi,Huizhe Wu,Boxuan Simen Zhao,Ana Mesquita,Chang Liu,Celvie L Yuan,Yueh-Chiang Hu,Stefan Hüttelmaier,Jennifer R Skibbe,Rui Su,Xiaolan Deng,Lei Dong,Miao Sun,Chenying Li,Sigrid Nachtergaele,Yungui Wang,Chao Hu,Kyle Ferchen,Kenneth D Greis,Xi Jiang,Minjie Wei,Lianghu Qu,Jun-Lin Guan,Chuan He,Jianhua Yang,Jianjun Chen

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-08-27
  • The hidden side of PD-L1.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-24
    Alison Jaccard,Ping-Chih Ho

    PD-L1 has been extensively described as the membrane-bound ligand of PD-1. A recent study discovered a previously unknown role for PD-L1, which is able to bind DNA and thus govern different pathways linked to either evasion of immune surveillance or tumour microenvironment inflammation.

    更新日期:2020-08-24
  • Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-24
    Yang Gao,Naoe Taira Nihira,Xia Bu,Chen Chu,Jinfang Zhang,Aleksandra Kolodziejczyk,Yizeng Fan,Ngai Ting Chan,Leina Ma,Jing Liu,Dong Wang,Xiaoming Dai,Huadong Liu,Masaya Ono,Akira Nakanishi,Hiroyuki Inuzuka,Brian J North,Yu-Han Huang,Samanta Sharma,Yan Geng,Wei Xu,X Shirley Liu,Lei Li,Yoshio Miki,Piotr Sicinski,Gordon J Freeman,Wenyi Wei

    Immunotherapies that target programmed cell death protein 1 (PD-1) and its ligand PD-L1 as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) have shown impressive clinical outcomes for multiple tumours. However, only a subset of patients achieves durable responses, suggesting that the mechanisms of the immune checkpoint pathways are not completely understood. Here, we report that PD-L1 translocates

    更新日期:2020-08-24
  • Epigenetic silencing of the ubiquitin ligase subunit FBXL7 impairs c-SRC degradation and promotes epithelial-to-mesenchymal transition and metastasis.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-24
    Loredana Moro,Daniele Simoneschi,Emma Kurz,Arnaldo A Arbini,Shaowen Jang,Nicoletta Guaragnella,Sergio Giannattasio,Wei Wang,Yu-An Chen,Geoffrey Pires,Andrew Dang,Elizabeth Hernandez,Payal Kapur,Ankita Mishra,Aristotelis Tsirigos,George Miller,Jer-Tsong Hsieh,Michele Pagano

    Epigenetic plasticity is a pivotal factor that drives metastasis. Here, we show that the promoter of the gene that encodes the ubiquitin ligase subunit FBXL7 is hypermethylated in advanced prostate and pancreatic cancers, correlating with decreased FBXL7 mRNA and protein levels. Low FBXL7 mRNA levels are predictive of poor survival in patients with pancreatic and prostatic cancers. FBXL7 mediates the

    更新日期:2020-08-24
  • Cell–cell adhesion and 3D matrix confinement determine jamming transitions in breast cancer invasion
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-24
    Olga Ilina; Pavlo G. Gritsenko; Simon Syga; Jürgen Lippoldt; Caterina A. M. La Porta; Oleksandr Chepizhko; Steffen Grosser; Manon Vullings; Gert-Jan Bakker; Jörn Starruß; Peter Bult; Stefano Zapperi; Josef A. Käs; Andreas Deutsch; Peter Friedl

    Plasticity of cancer invasion and metastasis depends on the ability of cancer cells to switch between collective and single-cell dissemination, controlled by cadherin-mediated cell–cell junctions. In clinical samples, E-cadherin-expressing and -deficient tumours both invade collectively and metastasize equally, implicating additional mechanisms controlling cell–cell cooperation and individualization

    更新日期:2020-08-24
  • Decapping enzyme 1A breaks X-chromosome symmetry by controlling Tsix elongation and RNA turnover.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-17
    Eric Aeby,Hun-Goo Lee,Yong-Woo Lee,Andrea Kriz,Brian C Del Rosario,Hyun Jung Oh,Myriam Boukhali,Wilhelm Haas,Jeannie T Lee

    How allelic asymmetry is generated remains a major unsolved problem in epigenetics. Here we model the problem using X-chromosome inactivation by developing “BioRBP”, an enzymatic RNA-proteomic method that enables probing of low-abundance interactions and an allelic RNA-depletion and -tagging system. We identify messenger RNA-decapping enzyme 1A (DCP1A) as a key regulator of Tsix, a noncoding RNA implicated

    更新日期:2020-08-17
  • p27 controls Ragulator and mTOR activity in amino acid-deprived cells to regulate the autophagy-lysosomal pathway and coordinate cell cycle and cell growth.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-17
    Ada Nowosad,Pauline Jeannot,Caroline Callot,Justine Creff,Renaud Thierry Perchey,Carine Joffre,Patrice Codogno,Stephane Manenti,Arnaud Besson

    Autophagy is a catabolic process whereby cytoplasmic components are degraded within lysosomes, allowing cells to maintain energy homeostasis during nutrient depletion. Several studies reported that the CDK inhibitor p27Kip1 promotes starvation-induced autophagy by an unknown mechanism. Here we find that p27 controls autophagy via an mTORC1-dependent mechanism in amino acid-deprived cells. During prolonged

    更新日期:2020-08-17
  • UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-17
    Jiang Liu,Di Guan,Maogong Dong,Jingjing Yang,Haibin Wei,Qian Liang,Lizhi Song,Lu Xu,Junjie Bai,Cui Liu,Jian Mao,Qian Zhang,Junzhi Zhou,Xiaoying Wu,Miao Wang,Yu-Sheng Cong

    p53 is the most intensively studied tumour suppressor1. The regulation of p53 homeostasis is essential for its tumour-suppressive function2,3. Although p53 is regulated by an array of post-translational modifications, both during normal homeostasis and in stress-induced responses2,3,4, how p53 maintains its homeostasis remains unclear. UFMylation is a recently identified ubiquitin-like modification

    更新日期:2020-08-17
  • Author Correction: Mammalian Atg8 proteins and the autophagy factor IRGM control mTOR and TFEB at a regulatory node critical for responses to pathogens.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-12
    Suresh Kumar,Ashish Jain,Seong Won Choi,Gustavo Peixoto Duarte da Silva,Lee Allers,Michal H Mudd,Ryan Scott Peters,Jan Haug Anonsen,Tor-Erik Rusten,Michael Lazarou,Vojo Deretic

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-08-12
  • A transitional stem cell state in the lung.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-10
    Jamie M Verheyden,Xin Sun

    Studies of stem cell behaviour during regeneration have largely focused on understanding how cells make the choice between self-renewal and differentiation. It remains unclear whether cells undergo smooth transitions during differentiation or pause at selective intermediate states. Three studies now explore this question in lung regeneration.

    更新日期:2020-08-10
  • A bridge between melanoma cell states.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-03
    Nicole M Aiello-Couzo,Yibin Kang

    Cellular plasticity allows tumours to adapt to and overcome therapeutic challenges. A recent study uncovered the gene regulatory networks that govern cell states and phenotype switching in melanoma, opening up possibilities to therapeutically target cell states or phenotypic plasticity to render melanoma cells more vulnerable to treatment.

    更新日期:2020-08-03
  • ESCRTs cut some slack.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-03
    Robert C Piper

    In this issue of Nature Cell Biology, Mercier et al. show that acute changes in membrane tension may be a physiological trigger for ESCRT assembly, which drives membrane scission, luminal vesicle budding, and a wide array of other membrane remodelling events throughout the cell.

    更新日期:2020-08-03
  • Endosomal membrane tension regulates ESCRT-III-dependent intra-lumenal vesicle formation.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-03
    Vincent Mercier,Jorge Larios,Guillaume Molinard,Antoine Goujon,Stefan Matile,Jean Gruenberg,Aurélien Roux

    The plasma membrane tension strongly affects cell surface processes, such as migration, endocytosis and signalling. However, it is not known whether the membrane tension of organelles regulates their functions, notably intracellular traffic. The endosomal sorting complexes required for transport (ESCRT)-III complex is the major membrane remodelling complex that drives intra-lumenal-vesicle (ILV) formation

    更新日期:2020-08-03
  • Mammalian Atg8 proteins and the autophagy factor IRGM control mTOR and TFEB at a regulatory node critical for responses to pathogens.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-03
    Suresh Kumar,Ashish Jain,Seong Won Choi,Gustavo Peixoto Duarte da Silva,Lee Allers,Michal H Mudd,Ryan Scott Peters,Jan Haug Anonsen,Tor-Erik Rusten,Michael Lazarou,Vojo Deretic

    Autophagy is a homeostatic process with multiple functions in mammalian cells. Here, we show that mammalian Atg8 proteins (mAtg8s) and the autophagy regulator IRGM control TFEB, a transcriptional activator of the lysosomal system. IRGM directly interacted with TFEB and promoted the nuclear translocation of TFEB. An mAtg8 partner of IRGM, GABARAP, interacted with TFEB. Deletion of all mAtg8s or GABARAPs

    更新日期:2020-08-03
  • Robust gene expression programs underlie recurrent cell states and phenotype switching in melanoma.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-03
    Jasper Wouters,Zeynep Kalender-Atak,Liesbeth Minnoye,Katina I Spanier,Maxime De Waegeneer,Carmen Bravo González-Blas,David Mauduit,Kristofer Davie,Gert Hulselmans,Ahmad Najem,Michael Dewaele,Dennis Pedri,Florian Rambow,Samira Makhzami,Valerie Christiaens,Frederik Ceyssens,Ghanem Ghanem,Jean-Christophe Marine,Suresh Poovathingal,Stein Aerts

    Melanoma cells can switch between a melanocytic and a mesenchymal-like state. Scattered evidence indicates that additional intermediate state(s) may exist. Here, to search for such states and decipher their underlying gene regulatory network (GRN), we studied 10 melanoma cultures using single-cell RNA sequencing (RNA-seq) as well as 26 additional cultures using bulk RNA-seq. Although each culture exhibited

    更新日期:2020-08-03
  • Beth Levine 1960-2020.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-08-01
    Anna Katharina Simon,Noboru Mizushima

    更新日期:2020-08-01
  • Oncogenic splicing regulated by phase separation.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-07-27
    Bo Liu,Omar Abdel-Wahab

    There is increasing appreciation that many proteins self-aggregate in cells to form functional subcompartments, some of which exist as a separate liquid phase. A study now identifies the biophysical properties of AKAP95 protein condensates as critical for supporting cancer cell proliferation and RNA splicing.

    更新日期:2020-07-27
  • Biophysical properties of AKAP95 protein condensates regulate splicing and tumorigenesis.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-07-27
    Wei Li,Jing Hu,Bi Shi,Francesco Palomba,Michelle A Digman,Enrico Gratton,Hao Jiang

    It remains unknown if biophysical or material properties of biomolecular condensates regulate cancer. Here we show that AKAP95, a nuclear protein that regulates transcription and RNA splicing, plays an important role in tumorigenesis by supporting cancer cell growth and suppressing oncogene-induced senescence. AKAP95 forms phase-separated and liquid-like condensates in vitro and in nucleus. Mutations

    更新日期:2020-07-27
  • A pan-cancer analysis reveals nonstop extension mutations causing SMAD4 tumour suppressor degradation.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-07-27
    Sonam Dhamija,Chul Min Yang,Jeanette Seiler,Ksenia Myacheva,Maiwen Caudron-Herger,Angela Wieland,Mahmoud Abdelkarim,Yogita Sharma,Marisa Riester,Matthias Groß,Jochen Maurer,Sven Diederichs

    Nonstop or stop-loss mutations convert a stop into a sense codon, resulting in translation into the 3′ untranslated region as a nonstop extension mutation to the next in-frame stop codon or as a readthrough mutation into the poly-A tail. Nonstop mutations have been characterized in hereditary diseases, but not in cancer genetics. In a pan-cancer analysis, we curated and analysed 3,412 nonstop mutations

    更新日期:2020-07-27
  • Cell stretching is amplified by active actin remodelling to deform and recruit proteins in mechanosensitive structures.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-07-27
    Sophie Massou,Filipe Nunes Vicente,Franziska Wetzel,Amine Mehidi,Dan Strehle,Cecile Leduc,Raphaël Voituriez,Olivier Rossier,Pierre Nassoy,Grégory Giannone

    Detection and conversion of mechanical forces into biochemical signals controls cell functions during physiological and pathological processes. Mechanosensing is based on protein deformations and reorganizations, yet the molecular mechanisms are still unclear. Using a cell-stretching device compatible with super-resolution microscopy and single-protein tracking, we explored the nanoscale deformations

    更新日期:2020-07-27
  • Regulated IFN signalling preserves the stemness of intestinal stem cells by restricting differentiation into secretory-cell lineages.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-07-20
    Taku Sato,Shun Ishikawa,Jumpei Asano,Hirona Yamamoto,Masayuki Fujii,Toshiro Sato,Kouhei Yamamoto,Keisuke Kitagaki,Takumi Akashi,Ryuichi Okamoto,Toshiaki Ohteki

    Intestinal stem cells (ISCs) are located at the crypt base and fine-tune the balance of their self-renewal and differentiation1,2, but the physiological mechanism involved in regulating that balance remains unknown. Here we describe a transcriptional regulator that preserves the stemness of ISCs by restricting their differentiation into secretory-cell lineages. Interferon regulatory factor 2 (IRF2)

    更新日期:2020-07-20
  • Persistence of a regeneration-associated, transitional alveolar epithelial cell state in pulmonary fibrosis.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-07-13
    Yoshihiko Kobayashi,Aleksandra Tata,Arvind Konkimalla,Hiroaki Katsura,Rebecca F Lee,Jianhong Ou,Nicholas E Banovich,Jonathan A Kropski,Purushothama Rao Tata

    Stem cells undergo dynamic changes in response to injury to regenerate lost cells. However, the identity of transitional states and the mechanisms that drive their trajectories remain understudied. Using lung organoids, multiple in vivo repair models, single-cell transcriptomics and lineage tracing, we find that alveolar type-2 epithelial cells undergoing differentiation into type-1 cells acquire pre-alveolar

    更新日期:2020-07-13
  • Protein homeostasis from the outside in.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-07-08
    Brant M Webster,Holly K Gildea,Andrew Dillin

    Secretory proteins undergo multiple rounds of co- and post-translational quality control checks inside the cell, but how their integrity is maintained outside the cell is an emerging topic. A study establishes a model system to investigate how the extracellular proteome is protected and integrates its findings into existing immune pathways.

    更新日期:2020-07-08
  • Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-29
    Marina Vietri,Sebastian W Schultz,Aurélie Bellanger,Carl M Jones,Louise I Petersen,Camilla Raiborg,Ellen Skarpen,Christeen Ramane J Pedurupillay,Ingrid Kjos,Eline Kip,Romy Timmer,Ashish Jain,Philippe Collas,Roland L Knorr,Sushma N Grellscheid,Halim Kusumaatmaja,Andreas Brech,Francesca Micci,Harald Stenmark,Coen Campsteijn

    The ESCRT-III membrane fission machinery maintains the integrity of the nuclear envelope. Although primary nuclei resealing takes minutes, micronuclear envelope ruptures seem to be irreversible. Instead, micronuclear ruptures result in catastrophic membrane collapse and are associated with chromosome fragmentation and chromothripsis, complex chromosome rearrangements thought to be a major driving force

    更新日期:2020-06-29
  • Endocytic regulation of cellular ion homeostasis controls lysosome biogenesis.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-29
    Tania López-Hernández,Dmytro Puchkov,Eberhard Krause,Tanja Maritzen,Volker Haucke

    Lysosomes serve as cellular degradation and signalling centres that coordinate metabolism in response to intracellular cues and extracellular signals. Lysosomal capacity is adapted to cellular needs by transcription factors, such as TFEB and TFE3, which activate the expression of lysosomal and autophagy genes. Nuclear translocation and activation of TFEB are induced by a variety of conditions such

    更新日期:2020-06-29
  • Heterochromatin establishment during early mammalian development is regulated by pericentromeric RNA and characterized by non-repressive H3K9me3.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-29
    Adam Burton,Vincent Brochard,Carmen Galan,Elias R Ruiz-Morales,Quirze Rovira,Diego Rodriguez-Terrones,Kai Kruse,Stéphanie Le Gras,Vishnu S Udayakumar,Hang Gyeong Chin,André Eid,Xiaoyu Liu,Chenfei Wang,Shaorong Gao,Sriharsa Pradhan,Juan M Vaquerizas,Nathalie Beaujean,Thomas Jenuwein,Maria-Elena Torres-Padilla

    Following fertilization in mammals, the gametes are reprogrammed to create a totipotent zygote, a process that involves de novo establishment of chromatin domains. A major feature occurring during preimplantation development is the dramatic remodelling of constitutive heterochromatin, although the functional relevance of this is unknown. Here, we show that heterochromatin establishment relies on the

    更新日期:2020-06-29
  • In and out from senescence.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-26
    Sara Zumerle,Andrea Alimonti

    Cellular senescence has been widely recognised for decades as a stable arrest of cell proliferation. A recent study identifies senescence establishment and maintenance as a dynamic and reversible process regulated by (in)activation of a predetermined enhancer landscape controlled by the pioneer transcription factor AP-1.

    更新日期:2020-06-26
  • Starve a cold, and perhaps a cancer.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-25
    Daniel Haensel,Anthony E Oro

    Stem cells tightly link their metabolism to cell fate decisions; however, how cancers co-opt and bypass metabolic pathways for growth advantage remains unclear. New evidence in this issue highlights how cancer stem cells avoid epigenetically driven differentiation by shutting down endogenous serine synthesis and becoming serine auxotrophs.

    更新日期:2020-06-25
  • SPIN90 associates with mDia1 and the Arp2/3 complex to regulate cortical actin organization.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-22
    Luyan Cao,Amina Yonis,Malti Vaghela,Elias H Barriga,Priyamvada Chugh,Matthew B Smith,Julien Maufront,Geneviève Lavoie,Antoine Méant,Emma Ferber,Miia Bovellan,Art Alberts,Aurélie Bertin,Roberto Mayor,Ewa K Paluch,Philippe P Roux,Antoine Jégou,Guillaume Romet-Lemonne,Guillaume Charras

    Cell shape is controlled by the submembranous cortex, an actomyosin network mainly generated by two actin nucleators: the Arp2/3 complex and the formin mDia1. Changes in relative nucleator activity may alter cortical organization, mechanics and cell shape. Here we investigate how nucleation-promoting factors mediate interactions between nucleators. In vitro, the nucleation-promoting factor SPIN90 promotes

    更新日期:2020-06-23
  • Author Correction: STING and IRF3 in stromal fibroblasts enable sensing of genomic stress in cancer cells to undermine oncolytic viral therapy.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-18
    Esther N Arwert,Emma L Milford,Antonio Rullan,Stefanie Derzsi,Steven Hooper,Takuya Kato,David Mansfield,Alan Melcher,Kevin J Harrington,Erik Sahai

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-06-18
  • The protein kinase Akt acts as a coat adaptor in endocytic recycling.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-15
    Jia-Wei Hsu,Ming Bai,Kunhua Li,Jia-Shu Yang,Nam Chu,Philip A Cole,Michael J Eck,Jian Li,Victor W Hsu

    Coat proteins have a central role in vesicular transport by binding to cargoes for their sorting into intracellular pathways. Cargo recognition is mediated by components of the coat complex known as adaptor proteins1,2,3. We previously showed that Arf-GAP with coil-coil, ANK repeat and PH domain-containing protein 1 (ACAP1) functions as an adaptor for a clathrin coat complex that has a function in

    更新日期:2020-06-15
  • Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-15
    Bilal N Sheikh,Sukanya Guhathakurta,Tsz Hong Tsang,Marius Schwabenland,Gina Renschler,Benjamin Herquel,Vivek Bhardwaj,Herbert Holz,Thomas Stehle,Olga Bondareva,Nadim Aizarani,Omar Mossad,Oliver Kretz,Wilfried Reichardt,Aindrila Chatterjee,Laura J Braun,Julien Thevenon,Herve Sartelet,Thomas Blank,Dominic Grün,Dominik von Elverfeldt,Tobias B Huber,Dietmar Vestweber,Sergiy Avilov,Marco Prinz,Joerg M Buescher

    Mutations in chromatin-modifying complexes and metabolic enzymes commonly underlie complex human developmental syndromes affecting multiple organs. A major challenge is to determine how disease-causing genetic lesions cause deregulation of homeostasis in unique cell types. Here we show that neural-specific depletion of three members of the non-specific lethal (NSL) chromatin complex—Mof, Kansl2 or

    更新日期:2020-06-15
  • Dissecting intratumour heterogeneity of nodal B-cell lymphomas at the transcriptional, genetic and drug-response levels.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-15
    Tobias Roider,Julian Seufert,Alexey Uvarovskii,Felix Frauhammer,Marie Bordas,Nima Abedpour,Marta Stolarczyk,Jan-Philipp Mallm,Sophie A Herbst,Peter-Martin Bruch,Hyatt Balke-Want,Michael Hundemer,Karsten Rippe,Benjamin Goeppert,Martina Seiffert,Benedikt Brors,Gunhild Mechtersheimer,Thorsten Zenz,Martin Peifer,Björn Chapuy,Matthias Schlesner,Carsten Müller-Tidow,Stefan Fröhling,Wolfgang Huber,Simon Anders

    Tumour heterogeneity encompasses both the malignant cells and their microenvironment. While heterogeneity between individual patients is known to affect the efficacy of cancer therapy, most personalized treatment approaches do not account for intratumour heterogeneity. We addressed this issue by studying the heterogeneity of nodal B-cell lymphomas by single-cell RNA-sequencing and transcriptome-informed

    更新日期:2020-06-15
  • Author Correction: Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-11
    Dan Liao,Li Zhong,Junqiang Yin,Cuiling Zeng,Xin Wang,Xingchuan Huang,Jinna Chen,Hong Zhang,Ruhua Zhang,Xin-Yuan Guan,Xintao Shuai,Jianhua Sui,Song Gao,Wuguo Deng,Yi-Xin Zeng,Jing-Nan Shen,Jian Chen,Tiebang Kang

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-06-11
  • AP-1 imprints a reversible transcriptional programme of senescent cells.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-08
    Ricardo Iván Martínez-Zamudio,Pierre-François Roux,José Américo N L F de Freitas,Lucas Robinson,Gregory Doré,Bin Sun,Dimitri Belenki,Maja Milanovic,Utz Herbig,Clemens A Schmitt,Jesús Gil,Oliver Bischof

    Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here,

    更新日期:2020-06-08
  • Author Correction: A hypoxia-responsive TRAF6-ATM-H2AX signalling axis promotes HIF1α activation, tumorigenesis and metastasis.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-05
    Abdol-Hossein Rezaeian,Chien-Feng Li,Ching-Yuan Wu,Xian Zhang,Jorge Delacerda,M James You,Fei Han,Zhen Cai,Yun Seong Jeong,Guoxiang Jin,Liem Phan,Ping-Chieh Chou,Mong-Hong Lee,Mien-Chie Hung,Dos Sarbassov,Hui-Kuan Lin

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-06-05
  • Publisher Correction: ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-04
    Sarah Theresa Boyle,Valentina Poltavets,Jasreen Kular,Natasha Theresa Pyne,Jarrod John Sandow,Alexander Charles Lewis,Kendelle Joan Murphy,Natasha Kolesnikoff,Paul Andre Bartholomew Moretti,Melinda Nay Tea,Vinay Tergaonkar,Paul Timpson,Stuart Maxwell Pitson,Andrew Ian Webb,Robert John Whitfield,Angel Francisco Lopez,Marina Kochetkova,Michael Susithiran Samuel

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-06-04
  • STING and IRF3 in stromal fibroblasts enable sensing of genomic stress in cancer cells to undermine oncolytic viral therapy.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-01
    Esther N Arwert,Emma L Milford,Antonio Rullan,Stefanie Derzsi,Steven Hooper,Takuya Kato,David Mansfield,Alan Melcher,Kevin J Harrington,Erik Sahai

    Cancer-associated fibroblasts (CAFs) perform diverse roles and can modulate therapy responses1. The inflammatory environment within tumours also influences responses to many therapies, including the efficacy of oncolytic viruses2; however, the role of CAFs in this context remains unclear. Furthermore, little is known about the cell signalling triggered by heterotypic cancer cell–fibroblast contacts

    更新日期:2020-06-01
  • Assembly of a persistent apical actin network by the formin Frl/Fmnl tunes epithelial cell deformability.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-01
    Benoit Dehapiot,Raphaël Clément,Hervé Alégot,Gabriella Gazsó-Gerhát,Jean-Marc Philippe,Thomas Lecuit

    Tissue remodelling during Drosophila embryogenesis is notably driven by epithelial cell contractility. This behaviour arises from the Rho1–Rok-induced pulsatile accumulation of non-muscle myosin II pulling on actin filaments of the medioapical cortex. While recent studies have highlighted the mechanisms governing the emergence of Rho1–Rok–myosin II pulsatility, little is known about how F-actin organization

    更新日期:2020-06-01
  • Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-06-01
    Dan Liao,Li Zhong,Junqiang Yin,Cuiling Zeng,Xin Wang,Xingchuan Huang,Jinna Chen,Hong Zhang,Ruhua Zhang,Xin-Yuan Guan,Xintao Shuai,Jianhua Sui,Song Gao,Wuguo Deng,Yi-Xin Zeng,Jing-Nan Shen,Jian Chen,Tiebang Kang

    Osteosarcoma is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of osteosarcoma remain poorly understood. Here we identify exon–intron fusion genes in osteosarcoma cell lines and tissues. These fusion genes are derived from chromosomal translocations that juxtapose the coding region for

    更新日期:2020-06-01
  • ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-05-25
    Sarah Theresa Boyle,Valentina Poltavets,Jasreen Kular,Natasha Theresa Pyne,Jarrod John Sandow,Alexander Charles Lewis,Kendelle Joan Murphy,Natasha Kolesnikoff,Paul Andre Bartholomew Moretti,Melinda Nay Tea,Vinay Tergaonkar,Paul Timpson,Stuart Maxwell Pitson,Andrew Ian Webb,Robert John Whitfield,Angel Francisco Lopez,Marina Kochetkova,Michael Susithiran Samuel

    It is well accepted that cancers co-opt the microenvironment for their growth. However, the molecular mechanisms that underlie cancer–microenvironment interactions are still poorly defined. Here, we show that Rho-associated kinase (ROCK) in the mammary tumour epithelium selectively actuates protein-kinase-R-like endoplasmic reticulum kinase (PERK), causing the recruitment and persistent education of

    更新日期:2020-05-25
  • Extracellular serine controls epidermal stem cell fate and tumour initiation.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-05-25
    Sanjeethan C Baksh,Pavlina K Todorova,Shiri Gur-Cohen,Brian Hurwitz,Yejing Ge,Jesse S S Novak,Matthew T Tierney,June Dela Cruz-Racelis,Elaine Fuchs,Lydia W S Finley

    Tissue stem cells are the cell of origin for many malignancies. Metabolites regulate the balance between self-renewal and differentiation, but whether endogenous metabolic pathways or nutrient availability predispose stem cells towards transformation remains unknown. Here, we address this question in epidermal stem cells (EpdSCs), which are a cell of origin for squamous cell carcinoma. We find that

    更新日期:2020-05-25
  • Dynamin regulates the dynamics and mechanical strength of the actin cytoskeleton as a multifilament actin-bundling protein.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-05-25
    Ruihui Zhang,Donghoon M Lee,John R Jimah,Nathalie Gerassimov,Changsong Yang,Sangjoon Kim,Delgermaa Luvsanjav,Jonathan Winkelman,Marcel Mettlen,Michael E Abrams,Raghav Kalia,Peter Keene,Pratima Pandey,Benjamin Ravaux,Ji Hoon Kim,Jonathon A Ditlev,Guofeng Zhang,Michael K Rosen,Adam Frost,Neal M Alto,Margaret Gardel,Sandra L Schmid,Tatyana M Svitkina,Jenny E Hinshaw,Elizabeth H Chen

    The dynamin GTPase is known to bundle actin filaments, but the underlying molecular mechanism and physiological relevance remain unclear. Our genetic analyses revealed a function of dynamin in propelling invasive membrane protrusions during myoblast fusion in vivo. Using biochemistry, total internal reflection fluorescence microscopy, electron microscopy and cryo-electron tomography, we show that dynamin

    更新日期:2020-05-25
  • Enhancer reprogramming driven by high-order assemblies of transcription factors promotes phenotypic plasticity and breast cancer endocrine resistance.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-05-18
    Mingjun Bi,Zhao Zhang,Yi-Zhou Jiang,Pengya Xue,Hu Wang,Zhao Lai,Xiaoyong Fu,Carmine De Angelis,Yue Gong,Zhen Gao,Jianhua Ruan,Victor X Jin,Elisabetta Marangoni,Elodie Montaudon,Christopher K Glass,Wei Li,Tim Hui-Ming Huang,Zhi-Ming Shao,Rachel Schiff,Lizhen Chen,Zhijie Liu

    Acquired therapy resistance is a major problem for anticancer treatment, yet the underlying molecular mechanisms remain unclear. Using an established breast cancer cellular model, we show that endocrine resistance is associated with enhanced phenotypic plasticity, indicated by a general downregulation of luminal/epithelial differentiation markers and upregulation of basal/mesenchymal invasive markers

    更新日期:2020-05-18
  • A pliable ERα cistrome evades therapy.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-05-18
    Xiaoli S Wu,Christopher R Vakoc

    The transcription factor oestrogen receptor alpha (ERα) has long been targeted for therapeutic benefit in cancer, but drug resistance can emerge through a multitude of mechanisms. A study now reveals how the ERα cistrome can become reprogrammed to confer resistance to tamoxifen in breast cancer.

    更新日期:2020-05-18
  • Author Correction: Merkel cell polyomavirus activates LSD1-mediated blockade of non-canonical BAF to regulate transformation and tumorigenesis.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-05-15
    Donglim Esther Park,Jingwei Cheng,John P McGrath,Matthew Y Lim,Camille Cushman,Selene K Swanson,Michelle L Tillgren,Joao A Paulo,Prafulla C Gokhale,Laurence Florens,Michael P Washburn,Patrick Trojer,James A DeCaprio

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

    更新日期:2020-05-15
  • The HOIL-1L ligase modulates immune signalling and cell death via monoubiquitination of LUBAC.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-05-11
    Yasuhiro Fuseya,Hiroaki Fujita,Minsoo Kim,Fumiaki Ohtake,Akira Nishide,Katsuhiro Sasaki,Yasushi Saeki,Keiji Tanaka,Ryosuke Takahashi,Kazuhiro Iwai

    The linear ubiquitin chain assembly complex (LUBAC), which consists of HOIP, SHARPIN and HOIL-1L, promotes NF-κB activation and protects against cell death by generating linear ubiquitin chains. LUBAC contains two RING-IBR-RING (RBR) ubiquitin ligases (E3), and the HOIP RBR is responsible for catalysing linear ubiquitination. We found that HOIL-1L RBR plays a crucial role in regulating LUBAC. HOIL-1L

    更新日期:2020-05-11
  • BMP4 resets mouse epiblast stem cells to naive pluripotency through ZBTB7A/B-mediated chromatin remodelling.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-05-11
    Shengyong Yu,Chunhua Zhou,Shangtao Cao,Jiangping He,Baomei Cai,Kaixin Wu,Yue Qin,Xingnan Huang,Lizhan Xiao,Jing Ye,Shuyang Xu,Wenxiu Xie,Junqi Kuang,Shilong Chu,Jing Guo,He Liu,Wei Pang,Lin Guo,Mengying Zeng,Xiaoshan Wang,Rongping Luo,Chen Li,Guoqing Zhao,Bo Wang,Linlin Wu,Jiekai Chen,Jing Liu,Duanqing Pei

    BMP4 regulates a plethora of developmental processes, including the dorsal-ventral axis and neural patterning. Here, we report that BMP4 reconfigures the nuclear architecture during the primed-to-naive transition (PNT). We first established a BMP4-driven PNT and show that BMP4 orchestrates the chromatin accessibility dynamics during PNT. Among the loci opened early by BMP4, we identified Zbtb7a and