Featured
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Letter |
Identification of a retinoic acid-dependent haemogenic endothelial progenitor from human pluripotent stem cells
Luff et al. report a distinct human mesoderm cell population that generates definitive haemogenic endothelium in a retinoic acid-dependent manner, thus highlighting the dependence of haematopoietic ontogeny on retinoic acid-responsive mesoderm.
- Stephanie A. Luff
- , J. Philip Creamer
- & Christopher M. Sturgeon
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News & Views |
RIPK1 and RIPK3 form mosaic necrosomes
Necrosomes formed by RIPK1–RIPK3 mediate necroptosis. Super-resolution microscopy identifies the architectural features of necrosomes and provides mechanistic insights into the signalling from RIPK1 to RIPK3 when RIPK1 is activated to mediate necroptosis, and from RIPK3 to RIPK1 when RIPK3 is inhibited to mediate apoptosis.
- Weiwei Qi
- & Junying Yuan
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Letter |
A role for Flower and cell death in controlling morphogen gradient scaling
Merino et al. report that the cell-death factor Flower can control responses to morphogen gradients and thus has a role in gradient scaling.
- Marisa M. Merino
- , Carole Seum
- & Marcos Gonzalez-Gaitan
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Article |
Reversible phase separation of HSF1 is required for an acute transcriptional response during heat shock
Zhang, Shao and coworkers report that HSF1 forms small condensates at its target gene loci to promote their transcription during acute heat stress. The produced HSP70 proteins in turn disperse HSF1 condensates to shut off the heat-shock response.
- Hongchen Zhang
- , Shipeng Shao
- & Yujie Sun
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Article |
Mosaic composition of RIP1–RIP3 signalling hub and its role in regulating cell death
Chen et al. examine the cellular necrosome using STORM and uncover the rod-shaped structure formed by mosaics of RIP1 and RIP3 oligomers.
- Xin Chen
- , Rongfeng Zhu
- & Jiahuai Han
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Article |
YAP/TAZ drives cell proliferation and tumour growth via a polyamine–eIF5A hypusination–LSD1 axis
Li et al. show that YAP/TAZ directly promotes polyamine biosynthesis and activates eIF5A activity to upregulate LSD1 expression, thereby suppressing various genes including tumour suppressors to enhance tumour growth.
- Hongde Li
- , Bo-Kuan Wu
- & Duojia Pan
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Article |
Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and angiogenesis
Das et al. show that the copper transporter CTR1 functions as a redox sensor in endothelial cells. CTR1 is modified after redox stress, which induces CTR1–VEGFR2 complex formation and promotes VEGFR2 signalling and angiogenesis.
- Archita Das
- , Dipankar Ash
- & Masuko Ushio-Fukai
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Article |
The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1
Han et al. report that the Hippo pathway kinases LATS1 and LATS2 phosphorylate the heavy metal response transcription factor MTF1, leading to attenuation of heavy metal response gene transcription and cellular detoxification.
- Han Han
- , Hiroki J. Nakaoka
- & Wenqi Wang
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News & Views |
An RNA helicase swirls in lymphangiogenesis
How lymphatic vessels arise from veins is still poorly understood. A study reports the discovery of a ribosome biogenesis regulator Ddx21 as a previously unappreciated specific factor that is important for the first steps of lymphatic but not blood vessel development. The finding may lead to better strategies to selectively target lymphangiogenesis.
- Severin Mühleder
- & Rui Benedito
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Article |
The RNA helicase Ddx21 controls Vegfc-driven developmental lymphangiogenesis by balancing endothelial cell ribosome biogenesis and p53 function
Hogan and colleagues report that the RNA helicase Ddx21 mediates Vegfc-stimulated lymphangiogenesis during zebrafish development through controlling rDNA transcription and ribosome biogenesis in endothelial cells.
- Katarzyna Koltowska
- , Kazuhide S. Okuda
- & Benjamin M. Hogan
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News & Views |
Epigenetic remodelling upon FGFR inhibition
FGFR-altered triple negative breast cancer (TNBC) develops adaptive resistance to FGFR inhibitor therapy. A new study shows that sustained FGFR inhibition causes SWI/SNF complex eviction at YAP-recruited enhancers followed by increased mTORC1 activity. Dual inhibition of YAP or mTORC1 and FGFR has a synergistic effect on tumour growth.
- Krystal A. Orlando
- & Paul A. Wade
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Article |
FGFR-inhibitor-mediated dismissal of SWI/SNF complexes from YAP-dependent enhancers induces adaptive therapeutic resistance
Li et al. define an adaptive resistance mechanism against FGFR inhibitor treatment in breast cancer attributed to loss of BRG1 chromatin recruitment, reactivation of YAP-dependent enhancers and upregulation of amino acid-induced mTORC1 activity.
- Yihao Li
- , Xintao Qiu
- & Myles Brown
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Article |
TRIM15 and CYLD regulate ERK activation via lysine-63-linked polyubiquitination
Zhu et al. report that, in response to growth signals, ERK undergoes TRIM15-mediated lysine-63-linked ubiquitination, which facilitates ERK interaction with MEK and therefore enhances ERK activity.
- Guixin Zhu
- , Meenhard Herlyn
- & Xiaolu Yang
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Article |
Perinatal angiogenesis from pre-existing coronary vessels via DLL4–NOTCH1 signalling
Lu, Wang et al. show in mice that the pre-existing embryonic coronary plexus at the inner myocardium undergoes angiogenic expansion through DLL4–NOTCH1 signalling to vascularize the expanding myocardium.
- Pengfei Lu
- , Yidong Wang
- & Bin Zhou
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News & Views |
An inflammatory switch for stem cell plasticity
Tissue-resident stem cells are capable of remarkable plasticity in areas of tissue damage, where inflammatory cells accumulate as part of the reparative response. A study in the lung now provides critical insight on how inflammatory signals alter cell-to-cell Notch signalling within the airway niche to drive stem cell plasticity.
- Jaymin J. Kathiriya
- & Tien Peng
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News & Views |
Mitochondrial UPR through generations
Neuronal mitochondria perturbation elicits a mitochondrial unfolded protein response (UPRmt) in peripheral tissues cell non-autonomously, dependent on the Wnt signalling pathway. A study now reveals that a Wnt-mediated increase in maternally inherited mitochondria DNA is responsible for transgenerational UPRmt induced by neuronal mitochondria perturbation.
- Mooncheol Park
- & Meng C. Wang
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Article |
The memory of neuronal mitochondrial stress is inherited transgenerationally via elevated mitochondrial DNA levels
Zhang et al. report that the systemic mitochondrial unfolded protein response triggered by neuronal mitochondrial stress can be transmitted across multiple generations in Caenorhabditis elegans via a mechanism involving elevation in mitochondrial DNA levels in oocytes.
- Qian Zhang
- , Zihao Wang
- & Ye Tian
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Article |
CCM3 is a gatekeeper in focal adhesions regulating mechanotransduction and YAP/TAZ signalling
Wang et al. identify CCM3 as a negative regulator of YAP/TAZ activation and mechanotransduction in focal adhesions, with important roles in controlling mesenchymal/stromal stem cell differentiation and metastasis in mouse models of breast cancer.
- Shan Wang
- , Emelie Englund
- & Chris D. Madsen
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Letter |
Ankyrin G organizes membrane components to promote coupling of cell mechanics and glucose uptake
Salvi et al. show that GLUT1 is critical for glucose uptake in response to external forces and that ankyrin G is required to retain GLUT1 at sites of E-cadherin force transmission, linking mechanotransduction and glucose uptake.
- Alicia M. Salvi
- , Jennifer L. Bays
- & Kris A. DeMali
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News & Views |
STING condensates on ER limit IFN response
STING is a key player in the IFN response to cytosolic DNA, and its multimerization is commonly associated with activation of the pathway. A new study now shows that STING forms ‘puzzle’-like condensates to limit the IFN response and constrain antiviral immune activation.
- Liudmila Andreeva
- & Hao Wu
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Article |
The STING phase-separator suppresses innate immune signalling
Yu et al. identify that STING bicondensates occur in virus-infected cells, thereby restricting TBK1 activation and innate immunity.
- Xiaoyu Yu
- , Liyuan Zhang
- & Zhengfan Jiang
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Article |
Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling
Ponsioen et al. use a FRET‐based ERK biosensor EKAREN5 in patient‐derived organoids to show that EGFR activity amplifies signal transduction efficiency in KRAS or BRAF mutant MAPK pathways.
- Bas Ponsioen
- , Jasmin B. Post
- & Hugo J. G. Snippert
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Article |
TGF-β-induced DACT1 biomolecular condensates repress Wnt signalling to promote bone metastasis
Esposito et al. show that TGF-β-induced DACT1 forms biomolecular condensates that sequester CK2 to repress Wnt signalling and modulate bone metastasis in cancer.
- Mark Esposito
- , Cao Fang
- & Yibin Kang
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Article |
AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1
Shi et al. show that following adrenergic signalling, PKA phosphorylates AIDA, which in turn interacts with and promotes oxidation of UCP1 to regulate UCP1-dependent adaptive thermogenesis.
- Meng Shi
- , Xiao-Yu Huang
- & Sheng-Cai Lin
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Article |
Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR–STAT3 signalling
Gao et al. show that a secretory variant of E-cadherin encoded by a circular RNA directly activates EGFR and STAT3 signalling, thereby promoting glioma stem cell tumorigenicity.
- Xinya Gao
- , Xin Xia
- & Nu Zhang
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Technical Report |
Optogenetic manipulation of cellular communication using engineered myosin motors
Zhang et al. design optogenetically controlled artificial transport vehicles that can be activated reversibly to manipulate cargo transport, impede neurite development and functionally characterize filopodial networks in axolotls.
- Zijian Zhang
- , Nicolas Denans
- & Maria Barna
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Article |
Proteotoxic stress is a driver of the loser status and cell competition
Baumgartner et al. identify proteotoxic stress as the underlying cause of the loser status in a cell competition model caused by reduced autophagic, proteasomal flux and accumulation of protein aggregates.
- Michael E. Baumgartner
- , Michael P. Dinan
- & Eugenia Piddini
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Article
| Open AccessOpposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia
Chumduri, Gurumurthy et al. show that cervical squamous and columnar epithelia derive from two stem cell populations, regulated by opposing Wnt signals, and that a Wnt-repressive environment can induce metaplasia.
- Cindrilla Chumduri
- , Rajendra Kumar Gurumurthy
- & Thomas F. Meyer
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Article |
Haematopoietic stem cell-dependent Notch transcription is mediated by p53 through the Histone chaperone Supt16h
Espanola et al. show in zebrafish that Supt16h, a component of the FACT complex, regulates HSC development through an increase of p53, which promotes expression of phc1, a transcriptional repressor of Notch.
- Sophia G. Espanola
- , Hyemin Song
- & Yoonsung Lee
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News & Views |
A MAP for PI3K activation on endosomes
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.
- Alex G. Batrouni
- & Jeremy M. Baskin
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Article |
Phosphatidylinositol 3-kinase signalling is spatially organized at endosomal compartments by microtubule-associated protein 4
Intracellularly regulated PI3K activation. Thapa et al. find that phosphatidylinositol-3,4,5-trisphosphate generation and Akt activation occur at intracellular membranes, rather than the plasma membrane, and that this is mediated by MAP4, which controls PI3Kα localization to microtubules.
- Narendra Thapa
- , Mo Chen
- & Richard A. Anderson
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Article |
ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration
Aharonov et al. use in vivo genetic approaches to show that ErBB2-mediated YAP activation initiates epithelial–mesenchymal transition-like processes and dedifferentiation of cardiomyocytes to drive heart regeneration.
- Alla Aharonov
- , Avraham Shakked
- & Eldad Tzahor
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Article |
STAT3–BDNF–TrkB signalling promotes alveolar epithelial regeneration after lung injury
Paris et al. show that after injury or influenza infection alveolar type II cells signal via a STAT3–BDNF axis that activates the TrkB receptor on mesenchymal niche cells and enhances alveolar repair.
- Andrew J. Paris
- , Katharina E. Hayer
- & G. Scott Worthen
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Article |
p27 controls Ragulator and mTOR activity in amino acid-deprived cells to regulate the autophagy–lysosomal pathway and coordinate cell cycle and cell growth
Nowosad et al. show that during amino acid starvation, the cell-cycle inhibitor p27 binds LAMTOR1 on lysosomes to inhibit mTOR and promote autophagy, linking cell division and cell growth machineries.
- Ada Nowosad
- , Pauline Jeannot
- & Arnaud Besson
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Article |
Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature
Sheikh et al. show that deficiency in the lysine acetyltransferase MOF causes aberrant accumulation of fatty acids in neural cells, which in turn triggers inflammation in nearby pericytes, resulting in brain haemorrhaging.
- Bilal N. Sheikh
- , Sukanya Guhathakurta
- & Asifa Akhtar
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Letter |
STING and IRF3 in stromal fibroblasts enable sensing of genomic stress in cancer cells to undermine oncolytic viral therapy
Tumour fibroblasts influence oncolytic viral therapy. Arwert et al. show that transcytosis of cancer cells into fibroblasts activates STING and IRF3 to upregulate interferon-β1, eliciting a transcriptional program to reduce the effectiveness of oncolytic viral therapy.
- Esther N. Arwert
- , Emma L. Milford
- & Erik Sahai
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Article |
ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism
Boyle et al. show that ROCK upregulates PERK signalling in epithelia of breast cancer, thereby enhancing recruitment and function of cancer-associated fibroblasts through CRELD2 to promote tumourigenesis.
- Sarah Theresa Boyle
- , Valentina Poltavets
- & Michael Susithiran Samuel
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Article |
BMP4 resets mouse epiblast stem cells to naive pluripotency through ZBTB7A/B-mediated chromatin remodelling
Yu, Zhou, Cao, He et al. show that BMP4 reconfigures the nuclear architecture during the transition from primed to naive pluripotency by targeting Zbtb7a and Zbtb7b, which encode proteins that mediate the opening of naive chromatin loci.
- Shengyong Yu
- , Chunhua Zhou
- & Duanqing Pei
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Article |
In vitro capture and characterization of embryonic rosette-stage pluripotency between naive and primed states
Neagu, van Genderen and Escudero et al. show that simultaneous inhibition of WNT and MEK signalling maintains a naive-primed intermediate pluripotency state in vitro, which displays features of the mouse embryonic rosette.
- Alex Neagu
- , Emiel van Genderen
- & Derk ten Berge
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Article |
Tissue-resident ductal macrophages survey the mammary epithelium and facilitate tissue remodelling
Dawson et al. characterize a macrophage population associated with mammary ducts that are long lived, derive from embryonic precursors and have multiple roles in pregnancy, lactation, involution and cancer.
- Caleb A. Dawson
- , Bhupinder Pal
- & Jane E. Visvader
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Article |
Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells
Targeting resistant stem cells in leukaemia, Perry et al. show that doxorubicin at low doses decreases Akt-mediated β-catenin activity, downregulates expression of multiple immune-checkpoint genes and dampens tumorigenesis of leukaemia stem cells.
- John M. Perry
- , Fang Tao
- & Linheng Li
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Article |
Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signalling
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
- & Fabrice Lavial
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Article |
Phase separation of TAZ compartmentalizes the transcription machinery to promote gene expression
Wu et al. show that TAZ can undergo phase separation and the resulting condensates locally concentrate transcriptional activators to facilitate the expression of TAZ-controlled genes.
- Yi Lu
- , Tiantian Wu
- & Kunxin Luo
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Resource |
Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions
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
- & Oliver Rocks
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Article |
Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma
Tsang et al. show that copper modulates the activity of autophagic kinases ULK1/2 to control autophagy, and is required for KRASG12D-driven tumour growth and cancer survival in response to starvation.
- Tiffany Tsang
- , Jessica M. Posimo
- & Donita C. Brady
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Letter |
A negative-feedback loop maintains optimal chemokine concentrations for directional cell migration
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
- & Holger Knaut
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Article |
TBKBP1 and TBK1 form a growth factor signalling axis mediating immunosuppression and tumourigenesis
Zhu et al. show that, in response to growth factors, TBKBP1 recruits TBK1 to promote its activation by PKCθ, thereby facilitating mTORC1 activation, tumour-mediated immunosuppression and tumourigenesis.
- Lele Zhu
- , Yanchuan Li
- & Shao-Cong Sun
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Article |
Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression
Cai et al. show that YAP forms liquid-like condensates in the nucleus that compartmentalize YAP’s DNA binding cofactors and transcription co-activators to induce transcription of YAP-specific proliferation genes.
- Danfeng Cai
- , Daniel Feliciano
- & Jennifer Lippincott-Schwartz