Browse Articles

  • Article |

    Liu et al. show that cancer cells with high levels of SLC7A11 have increased dependency on the pentose phosphate pathway and consequently accumulate disulfide, and can be therapeutically targeted by limiting glucose supply.

    • Xiaoguang Liu
    • , Kellen Olszewski
    • , Yilei Zhang
    • , Esther W. Lim
    • , Jiejun Shi
    • , Xiaoshan Zhang
    • , Jie Zhang
    • , Hyemin Lee
    • , Pranavi Koppula
    • , Guang Lei
    • , Li Zhuang
    • , M. James You
    • , Bingliang Fang
    • , Wei Li
    • , Christian M. Metallo
    • , Masha V. Poyurovsky
    •  & Boyi Gan
  • Review Article |

    Groth and colleagues discuss recent advances in chromatin replication and maintenance across mitotic division, with emphasis on replication-coupled chromatin assembly and chromatin maturation post-replication.

    • Kathleen R. Stewart-Morgan
    • , Nataliya Petryk
    •  & Anja Groth
  • Letter |

    Hoffmann and colleagues report that the mammalian maternal-to-zygotic transition requires KDM4A-mediated removal of H3K9me3 from the broad H3K4me3 domains in oocytes.

    • Aditya Sankar
    • , Mads Lerdrup
    • , Adeel Manaf
    • , Jens Vilstrup Johansen
    • , Javier Martin Gonzalez
    • , Rehannah Borup
    • , Robert Blanshard
    • , Arne Klungland
    • , Klaus Hansen
    • , Claus Yding Andersen
    • , John Arne Dahl
    • , Kristian Helin
    •  & Eva R. Hoffmann
  • Article |

    Netrin-1, via precise Neo1/Unc5B stoichiometry, promotes naive pluripotency, embryonic stem cell self-renewal in combination with leukaemia inhibitory factor, and the formation of the mouse epiblast in vivo.

    • Aurélia Huyghe
    • , Giacomo Furlan
    • , Duygu Ozmadenci
    • , Christina Galonska
    • , Jocelyn Charlton
    • , Xavier Gaume
    • , Noémie Combémorel
    • , Christina Riemenschneider
    • , Nicolas Allègre
    • , Jenny Zhang
    • , Pauline Wajda
    • , Nicolas Rama
    • , Pauline Vieugué
    • , Isabelle Durand
    • , Marie Brevet
    • , Nicolas Gadot
    • , Thomas Imhof
    • , Bradley J. Merrill
    • , Manuel Koch
    • , Patrick Mehlen
    • , Claire Chazaud
    • , Alexander Meissner
    •  & Fabrice Lavial
  • Resource |

    Pijuan-Sala et al. present a comprehensive single-nucleus open chromatin map of early mouse embryogenesis and validate the role of ETS transcription factor FEV in endothelial identity in zebrafish.

    • Blanca Pijuan-Sala
    • , Nicola K. Wilson
    • , Jun Xia
    • , Xiaomeng Hou
    • , Rebecca L. Hannah
    • , Sarah Kinston
    • , Fernando J. Calero-Nieto
    • , Olivier Poirion
    • , Sebastian Preissl
    • , Feng Liu
    •  & Berthold Göttgens
  • Article |

    Lee, Mall et al. explore why the sequence-related transcription factors Myod1 and Ascl1 lead to different reprogramming outcomes when expressed in fibroblasts, despite binding similar targets.

    • Qian Yi Lee
    • , Moritz Mall
    • , Soham Chanda
    • , Bo Zhou
    • , Kylesh S. Sharma
    • , Katie Schaukowitch
    • , Juan M. Adrian-Segarra
    • , Sarah D. Grieder
    • , Michael S. Kareta
    • , Orly L. Wapinski
    • , Cheen Euong Ang
    • , Rui Li
    • , Thomas C. Südhof
    • , Howard Y. Chang
    •  & Marius Wernig
  • Letter |

    Santoriello, Sporrij et al. show that the progesterone receptor associates with RNA helicase DDX21 during nucleotide depletion, promotes its binding on chromatin and rescues efficient transcription in melanoma cells.

    • Cristina Santoriello
    • , Audrey Sporrij
    • , Song Yang
    • , Ryan A. Flynn
    • , Telmo Henriques
    • , Bilguujin Dorjsuren
    • , Eugenia Custo Greig
    • , Wyatt McCall
    • , Meredith E. Stanhope
    • , Maurizio Fazio
    • , Michael Superdock
    • , Asher Lichtig
    • , Isaac Adatto
    • , Brian J. Abraham
    • , Marian Kalocsay
    • , Michael Jurynec
    • , Yi Zhou
    • , Karen Adelman
    • , Eliezer Calo
    •  & Leonard I. Zon
  • News & Views |

    Post-translational histone modifications are important regulators of nuclear reprogramming. A study now reveals that histone lysine demethylase KDM4A-mediated H3K9me3 demethylation in mammalian oocytes is essential for zygotic genome activation and preimplantation development.

    • Julie Brind’Amour
    •  & Matthew C. Lorincz
  • News & Views |

    YAP and TAZ, paralogous mammalian genes, act as the key transcriptional effectors of the Hippo pathway. Two recent reports show that both YAP and TAZ form liquid–liquid phase-separated bodies that promote gene transcription by engaging in super-enhancers.

    • J. Matthew Franklin
    •  & Kun-Liang Guan
  • Resource |

    Müller et al. provide a comprehensive resource depicting cellular substrates, localization and interacting partners of RhoGEF and RhoGAP proteins regulating the canonical Rho family of GTPases.

    • Paul M. Müller
    • , Juliane Rademacher
    • , Richard D. Bagshaw
    • , Celina Wortmann
    • , Carolin Barth
    • , Jakobus van Unen
    • , Keziban M. Alp
    • , Girolamo Giudice
    • , Rebecca L. Eccles
    • , Louise E. Heinrich
    • , Patricia Pascual-Vargas
    • , Marta Sanchez-Castro
    • , Lennart Brandenburg
    • , Geraldine Mbamalu
    • , Monika Tucholska
    • , Lisa Spatt
    • , Maciej T. Czajkowski
    • , Robert-William Welke
    • , Sunqu Zhang
    • , Vivian Nguyen
    • , Trendelina Rrustemi
    • , Philipp Trnka
    • , Kiara Freitag
    • , Brett Larsen
    • , Oliver Popp
    • , Philipp Mertins
    • , Anne-Claude Gingras
    • , Frederick P. Roth
    • , Karen Colwill
    • , Chris Bakal
    • , Olivier Pertz
    • , Tony Pawson
    • , Evangelia Petsalaki
    •  & Oliver Rocks
  • Article |

    Zhao et al. show that H2AK119ub1 is propagated during cell division through positive feedback mediated by the variant PRC1 complex containing RYBP or YAF2 and promoted by histone H1-mediated chromatin compaction.

    • Jicheng Zhao
    • , Min Wang
    • , Luyuan Chang
    • , Juan Yu
    • , Aoqun Song
    • , Cuifang Liu
    • , Wenjun Huang
    • , Tiantian Zhang
    • , Xudong Wu
    • , Xiaohua Shen
    • , Bing Zhu
    •  & Guohong Li
  • News & Views |

    Piwi proteins are aberrantly induced in human tumours, but their function in cancer has been poorly understood. A study now shows that in the absence of piRNA loading, human PIWIL1 promotes pancreatic cancer metastasis by acting as a co-activator of the anaphase-promoting complex/cyclosome (APC/C) to degrade the cell-adhesion protein Pinin.

    • Fan Yao
    •  & Li Ma
  • Article |

    Li et al. report that PIWIL1 executes a piRNA-independent function in promoting pancreatic cancer metastasis. Mechanistically, PIWIL1 acts as a co-activator for the ubiquitin E3 ligase APC/C.

    • Feng Li
    • , Peng Yuan
    • , Ming Rao
    • , Chun-Hui Jin
    • , Wei Tang
    • , Ye-Fei Rong
    • , Yun-Ping Hu
    • , Fengjuan Zhang
    • , Tao Wei
    • , Qi Yin
    • , Tingbo Liang
    • , Ligang Wu
    • , Jinsong Li
    • , Dangsheng Li
    • , Yingbin Liu
    • , Wenhui Lou
    • , Shuang Zhao
    •  & Mo-Fang Liu
  • Article |

    Davis et al. demonstrate heterogeneous and distinct transcriptome programs in breast cancer micrometastasis associated with upregulated mitochondrial oxidative phosphorylation.

    • Ryan T. Davis
    • , Kerrigan Blake
    • , Dennis Ma
    • , Mari B. Ishak Gabra
    • , Grace A. Hernandez
    • , Anh T. Phung
    • , Ying Yang
    • , Dustin Maurer
    • , Austin E. Y. T. Lefebvre
    • , Hamad Alshetaiwi
    • , Zhengtao Xiao
    • , Juan Liu
    • , Jason W. Locasale
    • , Michelle A. Digman
    • , Eric Mjolsness
    • , Mei Kong
    • , Zena Werb
    •  & Devon A. Lawson
  • Technical Report |

    Yue, Zong, Li, Li, Zhang, Wu et al. introduce an in toto live-imaging system to track cardiac ventricle chamber formation at single-cell resolution for up to 1.5 days and digitally reconstruct cell dynamics.

    • Yanzhu Yue
    • , Weijian Zong
    • , Xin Li
    • , Jinghang Li
    • , Youdong Zhang
    • , Runlong Wu
    • , Yazui Liu
    • , Jiahao Cui
    • , Qianhao Wang
    • , Yunkun Bian
    • , Xianhong Yu
    • , Yao Liu
    • , Guangming Tan
    • , Yunfeng Zhang
    • , Gang Zhao
    • , Bin Zhou
    • , Liangyi Chen
    • , Wenlei Xiao
    • , Heping Cheng
    •  & Aibin He
  • News & Views |

    The lack of endogenous reporter lines is a bottleneck in the study of subcellular dynamics in human adult stem cell (ASC)-derived organoids. An approach using CRISPR–Cas9-mediated homology-independent organoid transgenesis (CRISPR–HOT) in ASC-derived organoids now narrows the gap between basic research and translational studies in human organoids.

    • Qiutan Yang
    • , Koen C. Oost
    •  & Prisca Liberali
  • Technical Report |

    Artegiani, Hendriks et al. describe a CRISPR–Cas9-based method to efficiently generate human knock-in organoids using non-homologous end joining to study rare intestinal cell types and human hepatocyte division.

    • Benedetta Artegiani
    • , Delilah Hendriks
    • , Joep Beumer
    • , Rutger Kok
    • , Xuan Zheng
    • , Indi Joore
    • , Susana Chuva de Sousa Lopes
    • , Jeroen van Zon
    • , Sander Tans
    •  & Hans Clevers
  • News & Views |

    Misfolded proteins in the endoplasmic reticulum (ER) are returned to the cytosol and destroyed by a process known as ER-associated degradation (ERAD). Hrd1 has been implicated as the channel that mediates the transport of ERAD substrates to the cytosol. A study demonstrates that Hrd1 is gated by autoubiquitination and a soluble ERAD substrate.

    • Miguel Betegon
    •  & Jeffrey L. Brodsky
  • Letter |

    Montagner et al. show that lung epithelial cells induce Sfrp2 expression and fibronectin fibril formation in disseminated breast cancer cells, thereby promoting their survival and latency in the lung.

    • Marco Montagner
    • , Rahul Bhome
    • , Steven Hooper
    • , Probir Chakravarty
    • , Xiao Qin
    • , Jahangir Sufi
    • , Ajay Bhargava
    • , Colin D. H. Ratcliffe
    • , Yutaka Naito
    • , Arianna Pocaterra
    • , Christopher J. Tape
    •  & Erik Sahai
  • News & Views |

    Gene editing holds promise for the treatment of cancers that are driven by well-characterised molecular alterations. A study now provides a proof of concept for the feasibility of in vivo gene editing to correct TERT mutations in glioblastoma, providing a platform for the direct manipulation of genetic alterations to reduce tumour growth.

    • Katie Troike
    •  & Justin D. Lathia
  • Technical Report |

    Kim et al. develop an optogenetic visualization approach that can rapidly and reversibly trap messenger RNA molecules in protein clusters, thereby restricting their access to ribosomes and dampening translation efficiency.

    • Na Yeon Kim
    • , Sangkyu Lee
    • , Jeonghye Yu
    • , Nury Kim
    • , Seong Su Won
    • , Hyerim Park
    •  & Won Do Heo
  • Letter |

    Li et al. demonstrate the efficacy of correcting the mutated TERT promoter using a programmable base editing, highlighting its ability to induce senescence, arrest and regression in brain tumour models.

    • Xinjian Li
    • , Xu Qian
    • , Bin Wang
    • , Yan Xia
    • , Yanhua Zheng
    • , Linyong Du
    • , Daqian Xu
    • , Dongming Xing
    • , Ronald A. DePinho
    •  & Zhimin Lu
  • Letter |

    Lau et al. quantify endogenous concentrations of the chemokine Cxcl12 and its binding affinity for its cognate receptor Cxcr4 in zebrafish embryos, uncovering a negative-feedback loop governing directional cell migration in vivo.

    • Stephanie Lau
    • , Anna Feitzinger
    • , Gayatri Venkiteswaran
    • , John Wang
    • , Stephen W. Lewellis
    • , Chad A. Koplinski
    • , Francis C. Peterson
    • , Brian F. Volkman
    • , Martin Meier-Schellersheim
    •  & Holger Knaut
  • Letter |

    Lee et al. show that, after nitrogen starvation and genetic interference with the architecture of nuclear pore complexes, nucleoporins are degraded by autophagy, constituting a quality-control step at the nuclear envelope.

    • Chia-Wei Lee
    • , Florian Wilfling
    • , Paolo Ronchi
    • , Matteo Allegretti
    • , Shyamal Mosalaganti
    • , Stefan Jentsch
    • , Martin Beck
    •  & Boris Pfander
  • Article |

    Lee et al. show that energy stress inhibits ferroptosis through AMPK activation and demonstrate a role for AMPK in ferroptosis-associated renal ischaemia–reperfusion injury in vivo.

    • Hyemin Lee
    • , Fereshteh Zandkarimi
    • , Yilei Zhang
    • , Jitendra Kumar Meena
    • , Jongchan Kim
    • , Li Zhuang
    • , Siddhartha Tyagi
    • , Li Ma
    • , Thomas F. Westbrook
    • , Gregory R. Steinberg
    • , Daisuke Nakada
    • , Brent R. Stockwell
    •  & Boyi Gan
  • News & Views |

    Understanding the metabolic rewiring of pancreatic ductal adenocarcinoma is an emerging strategy for identifying cancer-associated liabilities and improving treatment. A new study now elucidates the function of the transaminase BCAT2 in the early stages of tumor development, providing insights that could stimulate novel therapeutic strategies.

    • Mattia Falcone
    •  & Oliver D. K. Maddocks
  • Letter |

    Li et al. show that BCAA transaminase 2 enhances uptake and catabolism of branched-chain amino acids, thereby promoting development of pancreatic ductal adenocarcinoma harbouring KRAS mutations.

    • Jin-Tao Li
    • , Miao Yin
    • , Di Wang
    • , Jian Wang
    • , Ming-Zhu Lei
    • , Ye Zhang
    • , Ying Liu
    • , Lei Zhang
    • , Shao-Wu Zou
    • , Li-Peng Hu
    • , Zhi-Gang Zhang
    • , Yi-Ping Wang
    • , Wen-Yu Wen
    • , Hao-Jie Lu
    • , Zheng-Jun Chen
    • , Dan Su
    •  & Qun-Ying Lei
  • Article |

    The Hippo and mTORC1 pathways regulate growth control for proper organ development. Here, Gan et al. find that the Hippo pathway kinases LATS1 and LATS2 phosphorylate the mTORC1 component Raptor to attenuate mTORC1 activation.

    • Wenjian Gan
    • , Xiaoming Dai
    • , Xiangpeng Dai
    • , Jun Xie
    • , Shasha Yin
    • , Junjie Zhu
    • , Chen Wang
    • , Yuchen Liu
    • , Jianping Guo
    • , Min Wang
    • , Jing Liu
    • , Jia Hu
    • , Ryan J. Quinton
    • , Neil J. Ganem
    • , Pengda Liu
    • , John M. Asara
    • , Pier Paolo Pandolfi
    • , Yingzi Yang
    • , Zhigang He
    • , Guangping Gao
    •  & Wenyi Wei
  • Article |

    Sun et al. uncover a conserved mechanism by which ribosomes function in defining the position of pachytene piRNA formation on long single-stranded RNAs during spermatogenesis.

    • Yu H. Sun
    • , Jiang Zhu
    • , Li Huitong Xie
    • , Ziwei Li
    • , Rajyalakshmi Meduri
    • , Xiaopeng Zhu
    • , Chi Song
    • , Chen Chen
    • , Emiliano P. Ricci
    • , Zhiping Weng
    •  & Xin Zhiguo Li
  • News & Views |

    The ribosome decodes messenger RNAs and constructs proteins based on the genetic blueprint. Ribosomes also associate with non-coding RNAs, such as PIWI-interacting RNA (piRNA) precursors, during the meiotic pachytene stage. Intriguingly, the ribosome mediates pachytene piRNA biogenesis by guiding endonucleolytic cleavage of piRNA precursors.

    • Yuanhui Mao
    •  & Shu-Bing Qian
  • Letter |

    Gaglia et al. show, using single-cell imaging and analysis in human tumours, that phase transition of heat-shock factor 1 (HSF1) to form intranuclear stress bodies mediates cell-fate decisions underlying cell survival or death.

    • Giorgio Gaglia
    • , Rumana Rashid
    • , Clarence Yapp
    • , Gaurav N. Joshi
    • , Carmen G. Li
    • , Susan L. Lindquist
    • , Kristopher A. Sarosiek
    • , Luke Whitesell
    • , Peter K. Sorger
    •  & Sandro Santagata
  • News & Views |

    A mechanism of secretory autophagy explains aspects of the packaging of proteins and RNA into extracellular vesicles and paves the way to a better understanding of their biological roles and medical applications.

    • Janusz Rak
  • Article |

    Solinger et al. show that FERARI is a conserved tethering platform that mediates Rab11-dependent recycling at sorting endosomes.

    • Jachen A. Solinger
    • , Harun-Or Rashid
    • , Cristina Prescianotto-Baschong
    •  & Anne Spang
  • Article |

    Hu, Tan, Chia et al. identify negative elongation factor A as one of the earliest drivers of the mouse embryonic 2-cell-like state through interaction with Top2a, which mediates Dux expression.

    • Zhenhua Hu
    • , Dennis Eng Kiat Tan
    • , Gloryn Chia
    • , Haihan Tan
    • , Hwei Fen Leong
    • , Benjamin Jieming Chen
    • , Mei Sheng Lau
    • , Kelly Yu Sing Tan
    • , Xuezhi Bi
    • , Dongxiao Yang
    • , Ying Swan Ho
    • , Baojiang Wu
    • , Siqin Bao
    • , Esther Sook Miin Wong
    •  & Wee-Wei Tee
  • Article |

    Leidal et al. show that the LC3-conjugation pathway, which is part of the autophagy machinery, controls extracellular vesicle cargo loading and secretion of RNA-binding proteins.

    • Andrew M. Leidal
    • , Hector H. Huang
    • , Timothy Marsh
    • , Tina Solvik
    • , Dachuan Zhang
    • , Jordan Ye
    • , FuiBoon Kai
    • , Juliet Goldsmith
    • , Jennifer Y. Liu
    • , Yu-Hsin Huang
    • , Teresa Monkkonen
    • , Ariadne Vlahakis
    • , Eric J. Huang
    • , Hani Goodarzi
    • , Li Yu
    • , Arun P. Wiita
    •  & Jayanta Debnath
  • Article |

    Clairmont et al. find that the TRIP13 ATPase regulates REV7–Shieldin dissociation to promote homology-directed repair and suppress non-homologous end joining, and show the importance of PARPi resistance in BRCA1-deficient cancers.

    • Connor S. Clairmont
    • , Prabha Sarangi
    • , Karthikeyan Ponnienselvan
    • , Lucas D. Galli
    • , Isabelle Csete
    • , Lisa Moreau
    • , Guillaume Adelmant
    • , Dipanjan Chowdhury
    • , Jarrod A. Marto
    •  & Alan D. D’Andrea
  • Resource |

    Wang, Yu, Zhou, Song et al. profile cardiomyocytes and neighbouring cells from healthy adults and patients with heart failure and in recovery, and delineate their cellular compositions and interaction networks.

    • Li Wang
    • , Peng Yu
    • , Bingying Zhou
    • , Jiangping Song
    • , Zheng Li
    • , Mingzhi Zhang
    • , Guangran Guo
    • , Yin Wang
    • , Xiao Chen
    • , Leng Han
    •  & Shengshou Hu
  • News & Views |

    The molecular clock regulates the rhythmic transcription of myriad genes, leading to a circadian pattern of expression of the encoded proteins. A study demonstrates circadian regulation of expression of components of the protein secretory pathway, providing a mechanism to generate circadian patterns of secreted protein expression.

    • Thomas P. Burris
  • Article |

    Yahara et al. show that yolk-sac macrophages, which are derived from erythromyeloid progenitors, produce neonatal osteoclasts that support bone homeostasis and repair and also provide long-lasting osteoclasts in adult bone.

    • Yasuhito Yahara
    • , Tomasa Barrientos
    • , Yuning J. Tang
    • , Vijitha Puviindran
    • , Puviindran Nadesan
    • , Hongyuan Zhang
    • , Jason R. Gibson
    • , Simon G. Gregory
    • , Yarui Diao
    • , Yu Xiang
    • , Yawar J. Qadri
    • , Tomokazu Souma
    • , Mari L. Shinohara
    •  & Benjamin A. Alman