-
Author Correction: Optogenetic manipulation of cellular communication using engineered myosin motors Nat. Cell Biol. (IF 20.042) Pub Date : 2021-02-19 Zijian Zhang; Nicolas Denans; Yingfei Liu; Olena Zhulyn; Hannah D. Rosenblatt; Marius Wernig; Maria Barna
A Correction to this paper has been published: https://doi.org/10.1038/s41556-021-00650-9.
-
Publisher Correction: The T-box transcription factor Eomesodermin governs haemogenic competence of yolk sac mesodermal progenitors Nat. Cell Biol. (IF 20.042) Pub Date : 2021-02-11 Luke T. G. Harland; Claire S. Simon; Anna D. Senft; Ita Costello; Lucas Greder; Ivan Imaz-Rosshandler; Berthold Göttgens; John C. Marioni; Elizabeth K. Bikoff; Catherine Porcher; Marella F. T. R. de Bruijn; Elizabeth J. Robertson
A Correction to this paper has been published: https://doi.org/10.1038/s41556-021-00645-6.
-
TOR targets an RNA processing network to regulate facultative heterochromatin, developmental gene expression and cell proliferation Nat. Cell Biol. (IF 20.042) Pub Date : 2021-02-11 Yi Wei; Nathan N. Lee; Lixia Pan; Jothy Dhakshnamoorthy; Ling-Ling Sun; Martin Zofall; David Wheeler; Shiv I. S. Grewal
Cell proliferation and differentiation require signalling pathways that enforce appropriate and timely gene expression. We find that Tor2, the catalytic subunit of the TORC1 complex in fission yeast, targets a conserved nuclear RNA elimination network, particularly the serine and proline-rich protein Pir1, to control gene expression through RNA decay and facultative heterochromatin assembly. Phosphorylation
-
Tumour-regulated anorexia preceding cachexia Nat. Cell Biol. (IF 20.042) Pub Date : 2021-02-08 Gang Wang; Haiying Zhang; David Lyden
Anorexia commonly develops in patients with advanced cancer and is closely associated with cachexia. A new study shows that anorexia emerges earlier than cachexia in both Drosophila and mouse tumour models and that tumour-derived humoral factors induce anorexia by systemically dysregulating neuropeptides in the brain.
-
Tumour-derived Dilp8/INSL3 induces cancer anorexia by regulating feeding neuropeptides via Lgr3/8 in the brain Nat. Cell Biol. (IF 20.042) Pub Date : 2021-02-08 Eunbyul Yeom; Hyemi Shin; Wonbeak Yoo; Eunsung Jun; Seokho Kim; Seung Hyun Hong; Dae-Woo Kwon; Tae Hoon Ryu; Jae Myoung Suh; Song Cheol Kim; Kyu-Sun Lee; Kweon Yu
In patients with advanced-stage cancer, cancer-associated anorexia affects treatment success and patient survival. However, the underlying mechanism is poorly understood. Here, we show that Dilp8, a Drosophila homologue of mammalian insulin-like 3 peptide (INSL3), is secreted from tumour tissues and induces anorexia through the Lgr3 receptor in the brain. Activated Dilp8-Lgr3 signalling upregulated
-
Functional mechanisms and abnormalities of the nuclear lamina Nat. Cell Biol. (IF 20.042) Pub Date : 2021-02-08 Adam Karoutas; Asifa Akhtar
Alterations in nuclear shape are present in human diseases and ageing. A compromised nuclear lamina is molecularly interlinked to altered chromatin functions and genomic instability. Whether these alterations are a cause or a consequence of the pathological state are important questions in biology. Here, we summarize the roles of nuclear envelope components in chromatin organization, phase separation
-
Twinfilin uncaps filament barbed ends to promote turnover of lamellipodial actin networks Nat. Cell Biol. (IF 20.042) Pub Date : 2021-02-08 Markku Hakala; Hugo Wioland; Mari Tolonen; Tommi Kotila; Antoine Jegou; Guillaume Romet-Lemonne; Pekka Lappalainen
Coordinated polymerization of actin filaments provides force for cell migration, morphogenesis and endocytosis. Capping protein (CP) is a central regulator of actin dynamics in all eukaryotes. It binds to actin filament (F-actin) barbed ends with high affinity and slow dissociation kinetics to prevent filament polymerization and depolymerization. However, in cells, CP displays remarkably rapid dynamics
-
Author Correction: ALK phosphorylates SMAD4 on tyrosine to disable TGF-β tumour suppressor functions Nat. Cell Biol. (IF 20.042) Pub Date : 2021-02-02 Qianting Zhang; Mu Xiao; Shuchen Gu; Yongxian Xu; Ting Liu; Hao Li; Yi Yu; Lan Qin; Yezhang Zhu; Fenfang Chen; Yulong Wang; Chen Ding; Hongxing Wu; Hongbin Ji; Zhe Chen; Youli Zu; Stephen Malkoski; Yi Li; Tingbo Liang; Junfang Ji; Jun Qin; Pinglong Xu; Bin Zhao; Li Shen; Xia Lin; Xin-Hua Feng
A Correction to this paper has been published: https://doi.org/10.1038/s41556-021-00638-5.
-
Engineered myosins drive filopodial transport Nat. Cell Biol. (IF 20.042) Pub Date : 2021-02-01 Burcu Erdogan; Jessica L. Whited
Engineered, light-inducible artificial myosin motors enable selective and direct manipulation of filopodial extensions and provide refined tools to control intracellular cargo transport in vivo.
-
Optogenetic manipulation of cellular communication using engineered myosin motors Nat. Cell Biol. (IF 20.042) Pub Date : 2021-02-01 Zijian Zhang; Nicolas Denans; Yingfei Liu; Olena Zhulyn; Hannah D. Rosenblatt; Marius Wernig; Maria Barna
Cells achieve highly efficient and accurate communication through cellular projections such as neurites and filopodia, yet there is a lack of genetically encoded tools that can selectively manipulate their composition and dynamics. Here, we present a versatile optogenetic toolbox of artificial multi-headed myosin motors that can move bidirectionally within long cellular extensions and allow for the
-
Author Correction: Puma and p21 represent cooperating checkpoints limiting self-renewal and chromosomal instability of somatic stem cells in response to telomere dysfunction Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-28 Tobias Sperka; Zhangfa Song; Yohei Morita; Kodandaramireddy Nalapareddy; Luis Miguel Guachalla; André Lechel; Yvonne Begus-Nahrmann; Martin D. Burkhalter; Monika Mach; Falk Schlaudraff; Birgit Liss; Zhenyu Ju; Michael R. Speicher; K. Lenhard Rudolph
A Correction to this paper has been published: https://doi.org/10.1038/s41556-021-00633-w.
-
Ribosomopathy-associated mutations cause proteotoxic stress that is alleviated by TOR inhibition Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-25 Carles Recasens-Alvarez; Cyrille Alexandre; Joanna Kirkpatrick; Hisashi Nojima; David J. Huels; Ambrosius P. Snijders; Jean-Paul Vincent
Ribosomes are multicomponent molecular machines that synthesize all of the proteins of living cells. Most of the genes that encode the protein components of ribosomes are therefore essential. A reduction in gene dosage is often viable albeit deleterious and is associated with human syndromes, which are collectively known as ribosomopathies1,2,3. The cell biological basis of these pathologies has remained
-
Proteotoxic stress is a driver of the loser status and cell competition Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-25 Michael E. Baumgartner; Michael P. Dinan; Paul F. Langton; Iwo Kucinski; Eugenia Piddini
Cell competition allows winner cells to eliminate less fit loser cells in tissues. In Minute cell competition, cells with a heterozygous mutation in ribosome genes, such as RpS3+/− cells, are eliminated by wild-type cells. How cells are primed as losers is partially understood and it has been proposed that reduced translation underpins the loser status of ribosome mutant, or Minute, cells. Here, using
-
Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-18 Cindrilla Chumduri; Rajendra Kumar Gurumurthy; Hilmar Berger; Oliver Dietrich; Naveen Kumar; Stefanie Koster; Volker Brinkmann; Kirstin Hoffmann; Marina Drabkina; Panagiota Arampatzi; Dajung Son; Uwe Klemm; Hans-Joachim Mollenkopf; Hermann Herbst; Mandy Mangler; Jörg Vogel; Antoine-Emmanuel Saliba; Thomas F. Meyer
The transition zones of the squamous and columnar epithelia constitute hotspots for the emergence of cancer, often preceded by metaplasia, in which one epithelial type is replaced by another. It remains unclear how the epithelial spatial organization is maintained and how the transition zone niche is remodelled during metaplasia. Here we used single-cell RNA sequencing to characterize epithelial subpopulations
-
ALC1 links chromatin accessibility to PARP inhibitor response in homologous recombination-deficient cells Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-18 Priyanka Verma; Yeqiao Zhou; Zhendong Cao; Peter V. Deraska; Moniher Deb; Eri Arai; Weihua Li; Yue Shao; Laura Puentes; Yiwen Li; Sonali Patankar; Robert H. Mach; Robert B. Faryabi; Junwei Shi; Roger A. Greenberg
The response to poly(ADP-ribose) polymerase inhibitors (PARPi) is dictated by homologous recombination (HR) DNA repair and the abundance of lesions that trap PARP enzymes. It remains unclear, however, if the established role of PARP in promoting chromatin accessibility impacts viability in these settings. Using a CRISPR-based screen, we identified the PAR-binding chromatin remodeller ALC1/CHD1L as
-
Prostate cancer hijacks the microenvironment Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-08 Phillip Thienger; Mark A. Rubin
Prostate cancer is difficult to treat because of molecular, cellular and clinical heterogeneity. Using single-cell RNA sequencing, a recent study reveals unexpected transcriptomic reprograming in immune cells and non-immune components of the tumour microenvironment, which may lead to viable therapeutic approaches against prostate cancer.
-
LCK senses asparagine for T cell activation Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-08 Jana L. Raynor; Hongbo Chi
Amino acids are critical nutrients that contribute to metabolic and signalling pathways required to meet energy and biosynthetic demands in T cells. A new study now demonstrates that LCK can sense intracellular asparagine to support T cell receptor-mediated CD8+ T cell activation and effector responses to pathogens and tumours.
-
Challenges to making an egg Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-08 Richard M. Schultz; John J. Eppig
Assembling egg cells involves cytoplasmic and nuclear processes that together enable embryonic development. A study now defines a set of transcription factors required for cytoplasmic, but not key nuclear, processes.
-
Evaluating totipotency using criteria of increasing stringency Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-08 Eszter Posfai; John Paul Schell; Adrian Janiszewski; Isidora Rovic; Alexander Murray; Brian Bradshaw; Tatsuya Yamakawa; Tine Pardon; Mouna El Bakkali; Irene Talon; Natalie De Geest; Pankaj Kumar; San Kit To; Sophie Petropoulos; Andrea Jurisicova; Vincent Pasque; Fredrik Lanner; Janet Rossant
Totipotency is the ability of a single cell to give rise to all of the differentiated cell types that build the conceptus, yet how to capture this property in vitro remains incompletely understood. Defining totipotency relies on a variety of assays of variable stringency. Here, we describe criteria to define totipotency. We explain how distinct criteria of increasing stringency can be used to judge
-
CRISPR technologies for precise epigenome editing Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-08 Muneaki Nakamura; Yuchen Gao; Antonia A. Dominguez; Lei S. Qi
The epigenome involves a complex set of cellular processes governing genomic activity. Dissecting this complexity necessitates the development of tools capable of specifically manipulating these processes. The repurposing of prokaryotic CRISPR systems has allowed for the development of diverse technologies for epigenome engineering. Here, we review the state of currently achievable epigenetic manipulations
-
The T-box transcription factor Eomesodermin governs haemogenic competence of yolk sac mesodermal progenitors Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-08 Luke T. G. Harland; Claire S. Simon; Anna D. Senft; Ita Costello; Lucas Greder; Ivan Imaz-Rosshandler; Berthold Göttgens; John C. Marioni; Elizabeth K. Bikoff; Catherine Porcher; Marella F. T. R. de Bruijn; Elizabeth J. Robertson
Extra-embryonic mesoderm (ExM)—composed of the earliest cells that traverse the primitive streak—gives rise to the endothelium as well as haematopoietic progenitors in the developing yolk sac. How a specific subset of ExM becomes committed to a haematopoietic fate remains unclear. Here we demonstrate using an embryonic stem cell model that transient expression of the T-box transcription factor Eomesodermin
-
Asparagine enhances LCK signalling to potentiate CD8 + T-cell activation and anti-tumour responses Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-08 Jun Wu; Gen Li; Le Li; Dan Li; Zhongjun Dong; Peng Jiang
Nutrient availability is central for T-cell functions and immune responses. Here we report that CD8+ T-cell activation and anti-tumour responses are strongly potentiated by the non-essential amino acid Asn. Increased Asn levels enhance CD8+ T-cell activation and effector functions against tumour cells in vitro and in vivo. Conversely, restriction of dietary Asn, ASNase administration or inhibition
-
Loss of the fragile X syndrome protein FMRP results in misregulation of nonsense-mediated mRNA decay Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-08 Tatsuaki Kurosaki; Naoto Imamachi; Christoph Pröschel; Shuhei Mitsutomi; Rina Nagao; Nobuyoshi Akimitsu; Lynne E. Maquat
Loss of the fragile X protein FMRP is a leading cause of intellectual disability and autism1,2, but the underlying mechanism remains poorly understood. We report that FMRP deficiency results in hyperactivated nonsense-mediated mRNA decay (NMD)3,4 in human SH-SY5Y neuroblastoma cells and fragile X syndrome (FXS) fibroblast-derived induced pluripotent stem cells (iPSCs). We examined the underlying mechanism
-
Single-cell analysis reveals transcriptomic remodellings in distinct cell types that contribute to human prostate cancer progression Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-08 Sujun Chen; Guanghui Zhu; Yue Yang; Fubo Wang; Yu-Tian Xiao; Na Zhang; Xiaojie Bian; Yasheng Zhu; Yongwei Yu; Fei Liu; Keqin Dong; Javier Mariscal; Yin Liu; Fraser Soares; Helen Loo Yau; Bo Zhang; Weidong Chen; Chao Wang; Dai Chen; Qinghua Guo; Zhengfang Yi; Mingyao Liu; Michael Fraser; Daniel D. De Carvalho; Paul C. Boutros; Dolores Di Vizio; Zhou Jiang; Theodorus van der Kwast; Alejandro Berlin;
Prostate cancer shows remarkable clinical heterogeneity, which manifests in spatial and clonal genomic diversity. By contrast, the transcriptomic heterogeneity of prostate tumours is poorly understood. Here we have profiled the transcriptomes of 36,424 single cells from 13 prostate tumours and identified the epithelial cells underlying disease aggressiveness. The tumour microenvironment (TME) showed
-
Non-canonical Wnt/PCP signalling regulates intestinal stem cell lineage priming towards enteroendocrine and Paneth cell fates Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-04 Anika Böttcher; Maren Büttner; Sophie Tritschler; Michael Sterr; Alexandra Aliluev; Lena Oppenländer; Ingo Burtscher; Steffen Sass; Martin Irmler; Johannes Beckers; Christoph Ziegenhain; Wolfgang Enard; Andrea C. Schamberger; Fien M. Verhamme; Oliver Eickelberg; Fabian J. Theis; Heiko Lickert
A detailed understanding of intestinal stem cell (ISC) self-renewal and differentiation is required to treat chronic intestinal diseases. However, the different models of ISC lineage hierarchy1,2,3,4,5,6 and segregation7,8,9,10,11,12 are subject to debate. Here, we have discovered non-canonical Wnt/planar cell polarity (PCP)-activated ISCs that are primed towards the enteroendocrine or Paneth cell
-
Endogenous promoter-driven sgRNA for monitoring the expression of low-abundance transcripts and lncRNAs Nat. Cell Biol. (IF 20.042) Pub Date : 2021-01-04 Ni Gao; Jing Hu; Bingbing He; Zhengbang Ji; Xinde Hu; Jia Huang; Yu Wei; Jianpeng Peng; Yinghui Wei; Yingsi Zhou; Xiaowen Shen; He Li; Xue Feng; Qingquan Xiao; Linyu Shi; Yidi Sun; Changyang Zhou; Haibo Zhou; Hui Yang
Detection of endogenous signals and precise control of genetic circuits in the natural context are essential to understand biological processes. However, the tools to process endogenous information are limited. Here we developed a generalizable endogenous transcription-gated switch that releases single-guide RNAs in the presence of an endogenous promoter. When the endogenous transcription-gated switch
-
Phase separation in plant miRNA processing Nat. Cell Biol. (IF 20.042) Pub Date : 2020-12-14 Seung Cho Lee; Robert A. Martienssen
Nuclear dicing bodies were discovered in plants as subcellular droplets of a component of the Dicing complex, which is involved in microRNA production. Now they are revealed to be liquid–liquid phase-separated condensates with intrinsically disordered regions of the Dicing component SERRATE driving both phase separation and miRNA processing.
-
Publisher Correction: Heat stress activates YAP/TAZ to induce the heat shock transcriptome Nat. Cell Biol. (IF 20.042) Pub Date : 2020-12-11 Min Luo; Zhipeng Meng; Toshiro Moroishi; Kimberly C. Lin; Guobo Shen; Fei Mo; Bin Shao; Xiawei Wei; Ping Zhang; Yuquan Wei; Kun-Liang Guan
A Correction to this paper has been published: https://doi.org/10.1038/s41556-020-00623-4.
-
Phase separation of SERRATE drives dicing body assembly and promotes miRNA processing in Arabidopsis Nat. Cell Biol. (IF 20.042) Pub Date : 2020-12-07 Dongqi Xie; Min Chen; Jinrong Niu; Liang Wang; Yan Li; Xiaofeng Fang; Pilong Li; Yijun Qi
MicroRNA (miRNA) production entails the step-wise processing of primary miRNAs (pri-miRNAs) into precursor miRNAs (pre-miRNAs) and miRNA/* duplexes by Dicing complexes containing DCL1, HYL1 and SE, which are localized in nuclear dicing bodies (D-bodies)1,2. Here, we show that D-bodies are phase-separated condensates. SE forms droplets and drives DCL1, HYL1 and pri/pre-miRNAs into the droplets in vitro
-
Many XCI-ting routes to reach the eXACT dose Nat. Cell Biol. (IF 20.042) Pub Date : 2020-11-30 Jean-François Ouimette; Claire Rougeulle
X-chromosome inactivation studies have revealed striking species specificities in terms of the players, kinetics and mechanisms. Transcriptomic profiling of human pre‐implantation development and germ cell differentiation suggests a peculiar dosage compensation mechanism with yet undefined contributions from XIST and XACT lncRNAs.
-
Female human primordial germ cells display X-chromosome dosage compensation despite the absence of X-inactivation Nat. Cell Biol. (IF 20.042) Pub Date : 2020-11-30 Tsotne Chitiashvili; Iris Dror; Rachel Kim; Fei-Man Hsu; Rohan Chaudhari; Erica Pandolfi; Di Chen; Simone Liebscher; Katja Schenke-Layland; Kathrin Plath; Amander Clark
X-chromosome dosage compensation in female placental mammals is achieved by X-chromosome inactivation (XCI). Human pre-implantation embryos are an exception, in which dosage compensation occurs by X-chromosome dampening (XCD). Here, we examined whether XCD extends to human prenatal germ cells given their similarities to naive pluripotent cells. We found that female human primordial germ cells (hPGCs)
-
Nuclear F-actin counteracts nuclear deformation and promotes fork repair during replication stress Nat. Cell Biol. (IF 20.042) Pub Date : 2020-11-30 Noa Lamm; Mark N. Read; Max Nobis; David Van Ly; Scott G. Page; V. Pragathi Masamsetti; Paul Timpson; Maté Biro; Anthony J. Cesare
Filamentous actin (F-actin) provides cells with mechanical support and promotes the mobility of intracellular structures. Although F-actin is traditionally considered to be cytoplasmic, here we reveal that nuclear F-actin participates in the replication stress response. Using live and super-resolution imaging, we find that nuclear F-actin is polymerized in response to replication stress through a pathway
-
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
-
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
-
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
-
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
-
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.
-
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
-
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.
-
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
-
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
-
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
-
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
-
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.
-
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.
-
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
-
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
-
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.
-
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
-
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
-
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.
-
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
-
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
-
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
-
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
-
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
-
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.