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  • Haematopoietic stem cell-dependent Notch transcription is mediated by p53 through the Histone chaperone Supt16h
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-11-23
    Sophia G. Espanola; Hyemin Song; Eunjin Ryu; Aditya Saxena; Eun-Sun Kim; Jennifer E. Manegold; Chanond A. Nasamran; Debashis Sahoo; Chang-Kyu Oh; Cara Bickers; Unbeom Shin; Stephanie Grainger; Yong Hwan Park; Lauren Pandolfo; Mi-Sun Kang; Sukhyun Kang; Kyungjae Myung; Kimberly L. Cooper; Deborah Yelon; David Traver; Yoonsung Lee

    Haematopoietic stem and progenitor cells (HSPCs) have been the focus of developmental and regenerative studies, yet our understanding of the signalling events regulating their specification remains incomplete. We demonstrate that supt16h, a component of the Facilitates chromatin transcription (FACT) complex, is required for HSPC formation. Zebrafish supt16h mutants express reduced levels of Notch-signalling

    更新日期:2020-11-23
  • Manipulating niche composition limits damage to haematopoietic stem cells during Plasmodium infection
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-11-23
    Myriam L. R. Haltalli; Samuel Watcham; Nicola K. Wilson; Kira Eilers; Alexander Lipien; Heather Ang; Flora Birch; Sara Gonzalez Anton; Chiara Pirillo; Nicola Ruivo; Maria L. Vainieri; Constandina Pospori; Robert E. Sinden; Tiago C. Luis; Jean Langhorne; Ken R. Duffy; Berthold Göttgens; Andrew M. Blagborough; Cristina Lo Celso

    Severe infections are a major stress on haematopoiesis, where the consequences for haematopoietic stem cells (HSCs) have only recently started to emerge. HSC function critically depends on the integrity of complex bone marrow (BM) niches; however, what role the BM microenvironment plays in mediating the effects of infection on HSCs remains an open question. Here, using a murine model of malaria and

    更新日期:2020-11-23
  • Heat stress activates YAP/TAZ to induce the heat shock transcriptome
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-11-16
    Min Luo; Zhipeng Meng; Toshiro Moroishi; Kimberly C. Lin; Guobo Shen; Fei Mo; Bin Shao; Xiawei Wei; Ping Zhang; Yuquan Wei; Kun-Liang Guan

    The Hippo pathway plays critical roles in cell growth, differentiation, organ development and tissue homeostasis, whereas its dysregulation can lead to tumorigenesis. YAP and TAZ are transcription co-activators and represent the main downstream effectors of the Hippo pathway. Here, we show that heat stress induces a strong and rapid YAP dephosphorylation and activation. The effect of heat shock on

    更新日期:2020-11-16
  • Apoptosis in the fetal testis eliminates developmentally defective germ cell clones
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-11-16
    Daniel H. Nguyen; Bikem Soygur; Su-Ping Peng; Safia Malki; Guang Hu; Diana J. Laird

    Many germ cells are eliminated during development, long before oogenesis or spermatogenesis. In mouse fetal testes, the majority of germ cell apoptosis coincides with the onset of male differentiation, suggesting coordination of these processes. We studied fetal germ-cell fates and discovered that both apoptosis and differentiation initiate in clonally related clusters. Lineage tracing confirmed that

    更新日期:2020-11-16
  • A MAP for PI3K activation on endosomes
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-11-02
    Alex G. Batrouni; Jeremy M. Baskin

    PI3K–Akt signalling downstream of cell-surface receptor activation has long been thought to occur at the plasma membrane. However, surprising evidence now reveals activation of PI3Kα-mediated PI(3,4,5)P3 synthesis on endosomal membranes that is dependent upon the interaction of PI3Kα with the microtubule-associated protein MAP4.

    更新日期:2020-11-02
  • Phosphatidylinositol-3-OH kinase signalling is spatially organized at endosomal compartments by microtubule-associated protein 4
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-11-02
    Narendra Thapa; Mo Chen; Hudson T. Horn; Suyong Choi; Tianmu Wen; Richard A. Anderson

    The canonical model of agonist-stimulated phosphatidylinositol-3-OH kinase (PI3K)–Akt signalling proposes that PI3K is activated at the plasma membrane, where receptors are activated and phosphatidylinositol-4,5-bisphosphate is concentrated. Here we show that phosphatidylinositol-3,4,5-trisphosphate generation and activated Akt are instead largely confined to intracellular membranes upon receptor tyrosine

    更新日期:2020-11-02
  • H19 lncRNA to dystrophin’s rescue
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-26
    Morten Ritso; Michael A. Rudnicki

    There are many challenges in finding an effective, long-lasting and universal cure for the whole cohort of patients with Duchenne muscular dystrophy (DMD). The discovery of H19 lncRNA as a stabiliser of dystrophin may prove to be the missing link to the success of various rescue therapies proposed for treating DMD.

    更新日期:2020-10-28
  • The lncRNA H19 alleviates muscular dystrophy by stabilizing dystrophin
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-26
    Yaohua Zhang; Yajuan Li; Qingsong Hu; Yutao Xi; Zhen Xing; Zhao Zhang; Lisa Huang; Jianbo Wu; Ke Liang; Tina K. Nguyen; Sergey D. Egranov; Chengcao Sun; Zilong Zhao; David H. Hawke; Jin Li; Deqiang Sun; Jean J. Kim; Ping Zhang; Jie Cheng; Abid Farida; Mien-Chie Hung; Leng Han; Radbod Darabi; Chunru Lin; Liuqing Yang

    Dystrophin proteomic regulation in muscular dystrophies (MDs) remains unclear. We report that a long noncoding RNA (lncRNA), H19, associates with dystrophin and inhibits E3-ligase-dependent polyubiquitination at Lys 3584 (referred to as Ub-DMD) and its subsequent protein degradation. In-frame deletions in BMD and a DMD non-silent mutation (C3340Y) resulted in defects in the ability of the protein to

    更新日期:2020-10-28
  • FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-26
    Laura García-Prat; Eusebio Perdiguero; Sonia Alonso-Martín; Stefania Dell’Orso; Srikanth Ravichandran; Stephen R. Brooks; Aster H. Juan; Silvia Campanario; Kan Jiang; Xiaotong Hong; Laura Ortet; Vanessa Ruiz-Bonilla; Marta Flández; Victoria Moiseeva; Elena Rebollo; Mercè Jardí; Hong-Wei Sun; Antonio Musarò; Marco Sandri; Antonio del Sol; Vittorio Sartorelli; Pura Muñoz-Cánoves

    Tissue regeneration declines with ageing but little is known about whether this arises from changes in stem-cell heterogeneity. Here, in homeostatic skeletal muscle, we identify two quiescent stem-cell states distinguished by relative CD34 expression: CD34High, with stemness properties (genuine state), and CD34Low, committed to myogenic differentiation (primed state). The genuine-quiescent state is

    更新日期:2020-10-28
  • PLCγ1 suppression promotes the adaptation of KRAS-mutant lung adenocarcinomas to hypoxia
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-19
    Maria Saliakoura; Matteo Rossi Sebastiano; Chiara Pozzato; Florian H. Heidel; Tina M. Schnöder; Spasenija Savic Prince; Lukas Bubendorf; Paolo Pinton; Ralph A. Schmid; Johanna Baumgartner; Stefan Freigang; Sabina A. Berezowska; Alessandro Rimessi; Georgia Konstantinidou

    Mutant KRAS modulates the metabolic plasticity of cancer cells to confer a growth advantage during hypoxia, but the molecular underpinnings are largely unknown. Using a lipidomic screen, we found that PLCγ1 is suppressed during hypoxia in KRAS-mutant human lung adenocarcinoma cancer cell lines. Suppression of PLCγ1 in hypoxia promotes a less oxidative cancer cell metabolism state, reduces the formation

    更新日期:2020-10-19
  • ER-resident oxidoreductases are glycosylated and trafficked to the cell surface to promote matrix degradation by tumour cells
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-19
    Manon Ros; Anh Tuan Nguyen; Joanne Chia; Son Le Tran; Xavier Le Guezennec; Ruth McDowall; Sergey Vakhrushev; Henrik Clausen; Martin James Humphries; Frederic Saltel; Frederic André Bard

    Tumour growth and invasiveness require extracellular matrix (ECM) degradation and are stimulated by the GALA pathway, which induces protein O-glycosylation in the endoplasmic reticulum (ER). ECM degradation requires metalloproteases, but whether other enzymes are required is unclear. Here, we show that GALA induces the glycosylation of the ER-resident calnexin (Cnx) in breast and liver cancer. Glycosylated

    更新日期:2020-10-19
  • Author Correction: Extracellular serine controls epidermal stem cell fate and tumour initiation
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-12
    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

    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:2020-10-12
  • Proliferation and EMT trigger heart repair
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-12
    Ainara González-Iglesias; M. Angela Nieto

    Triggering heart repair after myocardial infarction is a challenge in regenerative medicine. A study now shows how ERBB2-mediated YAP activation promotes both cardiomyocyte proliferation and epithelial-to-mesenchymal transition (EMT) in adult mice. EMT initiates cardiomyocyte dedifferentiation and migration and together with proliferation promotes cardiac regeneration.

    更新日期:2020-10-12
  • ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-12
    Alla Aharonov; Avraham Shakked; Kfir Baruch Umansky; Alon Savidor; Alexander Genzelinakh; David Kain; Daria Lendengolts; Or-Yam Revach; Yuka Morikawa; Jixin Dong; Yishai Levin; Benjamin Geiger; James F. Martin; Eldad Tzahor

    Cardiomyocyte loss after injury results in adverse remodelling and fibrosis, inevitably leading to heart failure. The ERBB2–Neuregulin and Hippo–YAP signalling pathways are key mediators of heart regeneration, yet the crosstalk between them is unclear. We demonstrate that transient overexpression of activated ERBB2 in cardiomyocytes (OE CMs) promotes cardiac regeneration in a heart failure model. OE

    更新日期:2020-10-12
  • Gli1 + mesenchymal stromal cells form a pathological niche to promote airway progenitor metaplasia in the fibrotic lung
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-12
    Monica Cassandras; Chaoqun Wang; Jaymin Kathiriya; Tatsuya Tsukui; Peri Matatia; Michael Matthay; Paul Wolters; Ari Molofsky; Dean Sheppard; Hal Chapman; Tien Peng

    Aberrant epithelial reprogramming can induce metaplastic differentiation at sites of tissue injury that culminates in transformed barriers composed of scar and metaplastic epithelium. While the plasticity of epithelial stem cells is well characterized, the identity and role of the niche has not been delineated in metaplasia. Here, we show that Gli1+ mesenchymal stromal cells (MSCs), previously shown

    更新日期:2020-10-12
  • Author Correction: 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 : 2020-10-08
    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

    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:2020-10-08
  • The piRNA CHAPIR regulates cardiac hypertrophy by controlling METTL3-dependent N 6 -methyladenosine methylation of Parp10 mRNA
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-05
    Xiang-Qian Gao; Yu-Hui Zhang; Fang Liu; Murugavel Ponnusamy; Xue-Mei Zhao; Lu-Yu Zhou; Mei Zhai; Cui-Yun Liu; Xin-Min Li; Man Wang; Chan Shan; Pei-Pei Shan; Yin Wang; Yan-Han Dong; Li-Li Qian; Tao Yu; Jie Ju; Tao Wang; Kai Wang; Xin-Zhe Chen; Yun-Hong Wang; Jian Zhang; Pei-Feng Li; Kun Wang

    PIWI-interacting RNAs (piRNAs) are abundantly expressed during cardiac hypertrophy. However, their functions and molecular mechanisms remain unknown. Here, we identified a cardiac-hypertrophy-associated piRNA (CHAPIR) that promotes pathological hypertrophy and cardiac remodelling by targeting METTL3-mediated N6-methyladenosine (m6A) methylation of Parp10 mRNA transcripts. CHAPIR deletion markedly attenuates

    更新日期:2020-10-05
  • LRRC31 inhibits DNA repair and sensitizes breast cancer brain metastasis to radiation therapy
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-10-01
    Yanke Chen; Ting Jiang; Hongyi Zhang; Xingchun Gou; Cong Han; Jianhui Wang; Ann T. Chen; Jun Ma; Jun Liu; Zeming Chen; Xintao Jing; Hong Lei; Zhenzhen Wang; Youmei Bao; Mehdi Baqri; Yong Zhu; Ranjit S. Bindra; James E. Hansen; Jun Dou; Chen Huang; Jiangbing Zhou

    Breast cancer brain metastasis (BCBM) is a devastating disease. Radiation therapy remains the mainstay for treatment of this disease. Unfortunately, its efficacy is limited by the dose that can be safely applied. One promising approach to overcoming this limitation is to sensitize BCBMs to radiation by inhibiting their ability to repair DNA damage. Here, we report a DNA repair suppressor, leucine-rich

    更新日期:2020-10-02
  • Autophagy goes nuclear
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-28
    Jay X. Tan; Toren Finkel

    Sirtuins are highly conserved enzymes with key roles in life extension in multiple organisms. A study now describes selective autophagic degradation of nuclear SIRT1 in senescent cells. These observations suggest that blocking sirtuin degradation could be a potential approach for anti-ageing therapies.

    更新日期:2020-09-28
  • LC3 lipidation is essential for TFEB activation during the lysosomal damage response to kidney injury
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-28
    Shuhei Nakamura; Saki Shigeyama; Satoshi Minami; Takayuki Shima; Shiori Akayama; Tomoki Matsuda; Alessandra Esposito; Gennaro Napolitano; Akiko Kuma; Tomoko Namba-Hamano; Jun Nakamura; Kenichi Yamamoto; Miwa Sasai; Ayaka Tokumura; Mika Miyamoto; Yukako Oe; Toshiharu Fujita; Seigo Terawaki; Atsushi Takahashi; Maho Hamasaki; Masahiro Yamamoto; Yukinori Okada; Masaaki Komatsu; Takeharu Nagai; Yoshitsugu

    Sensing and clearance of dysfunctional lysosomes is critical for cellular homeostasis. Here we show that transcription factor EB (TFEB)—a master transcriptional regulator of lysosomal biogenesis and autophagy—is activated during the lysosomal damage response, and its activation is dependent on the function of the ATG conjugation system, which mediates LC3 lipidation. In addition, lysosomal damage triggers

    更新日期:2020-09-28
  • SIRT1 is downregulated by autophagy in senescence and ageing
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-28
    Caiyue Xu; Lu Wang; Parinaz Fozouni; Gry Evjen; Vemika Chandra; Jing Jiang; Congcong Lu; Michael Nicastri; Corey Bretz; Jeffrey D. Winkler; Ravi Amaravadi; Benjamin A. Garcia; Peter D. Adams; Melanie Ott; Wei Tong; Terje Johansen; Zhixun Dou; Shelley L. Berger

    SIRT1 (Sir2) is an NAD+-dependent deacetylase that plays critical roles in a broad range of biological events, including metabolism, the immune response and ageing1,2,3,4,5. Although there is strong interest in stimulating SIRT1 catalytic activity, the homeostasis of SIRT1 at the protein level is poorly understood. Here we report that macroautophagy (hereafter referred to as autophagy), a catabolic

    更新日期:2020-09-28
  • Mitochondrial RNA granules are fluid condensates positioned by membrane dynamics
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-28
    Timo Rey; Sofia Zaganelli; Emilie Cuillery; Evangelia Vartholomaiou; Marie Croisier; Jean-Claude Martinou; Suliana Manley

    Mitochondria contain the genetic information and expression machinery to produce essential respiratory chain proteins. Within the mitochondrial matrix, newly synthesized RNA, RNA processing proteins and mitoribosome assembly factors form punctate sub-compartments referred to as mitochondrial RNA granules (MRGs)1,2,3. Despite their proposed importance in regulating gene expression, the structural and

    更新日期:2020-09-28
  • Global hyperactivation of enhancers stabilizes human and mouse naive pluripotency through inhibition of CDK8/19 Mediator kinases
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-28
    Cian J. Lynch; Raquel Bernad; Ana Martínez-Val; Marta N. Shahbazi; Sandrina Nóbrega-Pereira; Isabel Calvo; Carmen Blanco-Aparicio; Carolina Tarantino; Elena Garreta; Laia Richart-Ginés; Noelia Alcazar; Osvaldo Graña-Castro; Gonzalo Gómez-Lopez; Irene Aksoy; Maribel Muñoz-Martín; Sonia Martinez; Sagrario Ortega; Susana Prieto; Elisabeth Simboeck; Alain Camasses; Camille Stephan-Otto Attolini; Agustin

    Pluripotent stem cells (PSCs) transition between cell states in vitro, reflecting developmental changes in the early embryo. PSCs can be stabilized in the naive state by blocking extracellular differentiation stimuli, particularly FGF–MEK signalling. Here, we report that multiple features of the naive state in human and mouse PSCs can be recapitulated without affecting FGF–MEK signalling or global

    更新日期:2020-09-28
  • STAT3–BDNF–TrkB signalling promotes alveolar epithelial regeneration after lung injury
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-28
    Andrew J. Paris; Katharina E. Hayer; Joseph H. Oved; Daphne C. Avgousti; Sushila A. Toulmin; Jarod A. Zepp; William J. Zacharias; Jeremy B. Katzen; Maria C. Basil; Madison M. Kremp; April R. Slamowitz; Sowmya Jayachandran; Aravind Sivakumar; Ning Dai; Ping Wang; David B. Frank; Laurence C. Eisenlohr; Edward Cantu; Michael F. Beers; Matthew D. Weitzman; Edward E. Morrisey; G. Scott Worthen

    Alveolar epithelial regeneration is essential for recovery from devastating lung diseases. This process occurs when type II alveolar pneumocytes (AT2 cells) proliferate and transdifferentiate into type I alveolar pneumocytes (AT1 cells). We used genome-wide analysis of chromatin accessibility and gene expression following acute lung injury to elucidate repair mechanisms. AT2 chromatin accessibility

    更新日期:2020-09-28
  • ERADicating stem cells from their niche.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-21
    Kentson Lam,Robert A J Signer

    Protein homeostasis preserves stem cell function, but the underlying mechanisms are largely unknown. A study reveals that protein quality control mediated by the endoplasmic reticulum-associated degradation pathway ensures proper expression of MPL, a key cell surface receptor that promotes haematopoietic stem cell function through niche interaction.

    更新日期:2020-09-21
  • Protein quality control through endoplasmic reticulum-associated degradation maintains haematopoietic stem cell identity and niche interactions.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-21
    Longyong Xu,Xia Liu,Fanglue Peng,Weijie Zhang,Liting Zheng,Yao Ding,Tianpeng Gu,Kaosheng Lv,Jin Wang,Laura Ortinau,Tianyuan Hu,Xiangguo Shi,Guojun Shi,Ge Shang,Shengyi Sun,Takao Iwawaki,Yewei Ji,Wei Li,Jeffrey M Rosen,Xiang H-F Zhang,Dongsu Park,Stanley Adoro,Andre Catic,Wei Tong,Ling Qi,Daisuke Nakada,Xi Chen

    Stem cells need to be protected from genotoxic and proteotoxic stress to maintain a healthy pool throughout life1,2,3. Little is known about the proteostasis mechanism that safeguards stem cells. Here we report endoplasmic reticulum-associated degradation (ERAD) as a protein quality checkpoint that controls the haematopoietic stem cell (HSC)–niche interaction and determines the fate of HSCs. The SEL1L–HRD1

    更新日期:2020-09-21
  • SMN-primed ribosomes modulate the translation of transcripts related to spinal muscular atrophy.
    Nat. Cell Biol. (IF 20.042) Pub Date : 2020-09-21
    Fabio Lauria,Paola Bernabò,Toma Tebaldi,Ewout Joan Nicolaas Groen,Elena Perenthaler,Federica Maniscalco,Annalisa Rossi,Deborah Donzel,Massimiliano Clamer,Marta Marchioretto,Neža Omersa,Julia Orri,Mauro Dalla Serra,Gregor Anderluh,Alessandro Quattrone,Alberto Inga,Thomas Henry Gillingwater,Gabriella Viero

    The contribution of ribosome heterogeneity and ribosome-associated proteins to the molecular control of proteomes in health and disease remains unclear. Here, we demonstrate that survival motor neuron (SMN) protein—the loss of which causes the neuromuscular disease spinal muscular atrophy (SMA)—binds to ribosomes and that this interaction is tissue-dependent. SMN-primed ribosomes are preferentially

    更新日期:2020-09-21
  • 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