{"title":"Sympathetic innervation maintains the murine quiescent skeletal muscle stem cell pool via perivascular-derived Angpt1","authors":"Alessio Rotini, Juliette Berthier, Ester Martínez-Sarrà, Gwladys Berge, Teoman Ozturk, Zeynab Koumaiha, Nathalie Didier, Sara Salucci, Olivier Stettler, Marianne Gervais, Romain K. Gherardi, Peggy Lafuste, Frédéric Relaix","doi":"10.1016/j.devcel.2025.07.006","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.006","url":null,"abstract":"Muscle stem cells rely on their niche for maintenance, yet how β-adrenergic innervation regulates these cells remains elusive. Here, we show that sympathetic fibers in skeletal muscle innervate the vascular stem cell niche, specifically targeting β-adrenergic receptors on perivascular cells. We observe that sympathetic denervation leads to vascular remodeling and, concomitantly, reduces the muscle stem cell pool, resulting in tissue repair defects. Mechanistically, we demonstrate that sympathetic denervation reduces perivascular-derived angiopoietin-1, a crucial factor in maintaining the quiescent state of post-natal muscle stem cells. Using pharmacologic and genetic tools, we identify that sympathetic signaling drives angiopoietin-1 production from murine perivascular cells through the stimulation of their β-adrenergic receptors, thereby preserving the quiescent stem cell pool. Collectively, our data identify the molecular and cellular axis coupling skeletal muscle tissue homeostasis and regeneration to sympathetic innervation and β-adrenergic signaling, which are thus key signaling pathways that contribute to satellite cell quiescence.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"723 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-07-30DOI: 10.1016/j.devcel.2025.07.003
Xiaowei Wu, Songyao Zhang, Tingting Su, Yu Zhang, Chui Eng Wong, Lisha Shen, Hao Yu
{"title":"Temperature-responsive N4-acetylcytidine mRNA modification controls thermosensory flowering in Arabidopsis","authors":"Xiaowei Wu, Songyao Zhang, Tingting Su, Yu Zhang, Chui Eng Wong, Lisha Shen, Hao Yu","doi":"10.1016/j.devcel.2025.07.003","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.07.003","url":null,"abstract":"<em>N</em><sup>4</sup>-acetylcytidine (ac<sup>4</sup>C) represents the only acetylation modification on eukaryotic mRNAs. Although ac<sup>4</sup>C mRNA modification has been recently identified in plants, its biological function in plant response to environmental signals and related underlying mechanisms remain elusive. Here, we show that two ac<sup>4</sup>C writers, <em>N</em>-acetyltransferase 10A (NAT10A) and NAT10B, determine thermosensory flowering in <em>Arabidopsis</em> by mediating ac<sup>4</sup>C deposition on the transcripts of <em>FLOWERING LOCUS M</em> (<em>FLM</em>) and their temperature-dependent alternative splicing. NAT10A and NAT10B are rapidly induced by low ambient temperature, resulting in a transcriptome-wide increase in ac<sup>4</sup>C modification on target transcripts, including <em>FLM</em>. Consequently, elevated ac<sup>4</sup>C on nascent <em>FLM</em> transcripts impedes the binding of SPLICING FACTOR 1 to <em>FLM</em> to favor the production of the splice variants <em>FLM-δ</em> versus <em>FLM-β</em>, thereby preventing extremely late flowering at low ambient temperature. These findings demonstrate that ac<sup>4</sup>C RNA modification constitutes an integral part of the flowering regulatory network that effectively responds to changing temperatures.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"139 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-07-24DOI: 10.1016/j.devcel.2025.06.031
John E.G. Lawrence, Steven Woods, Kenny Roberts, Dinithi Sumanaweera, Petra Balogh, Tong Li, Alexander V. Predeus, Peng He, Krzysztof Polanski, Elena Prigmore, Elizabeth Tuck, Lira Mamanova, Di Zhou, Simone Webb, Laura Jardine, Xiaoling He, Roger A. Barker, Muzlifah Haniffa, Adrienne M. Flanagan, Matthew J. Young, Sarah A. Teichmann
{"title":"Single-cell transcriptomics identifies chondrocyte differentiation dynamics in vivo and in vitro","authors":"John E.G. Lawrence, Steven Woods, Kenny Roberts, Dinithi Sumanaweera, Petra Balogh, Tong Li, Alexander V. Predeus, Peng He, Krzysztof Polanski, Elena Prigmore, Elizabeth Tuck, Lira Mamanova, Di Zhou, Simone Webb, Laura Jardine, Xiaoling He, Roger A. Barker, Muzlifah Haniffa, Adrienne M. Flanagan, Matthew J. Young, Sarah A. Teichmann","doi":"10.1016/j.devcel.2025.06.031","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.031","url":null,"abstract":"Developing <em>in vitro</em> chondrocytes that replicate <em>in vivo</em> development would benefit musculoskeletal disease modeling and regenerative medicine. Although current methodologies have made progress, challenges such as off-target differentiation can result in heterogeneous cell states. Furthermore, the lack of comparison with human embryonic tissue precludes detailed evaluation of <em>in vitro</em> cells. Here, we perform single-cell RNA sequencing (scRNA-seq) of embryonic long bones and combine this with public data to form an atlas of endochondral ossification. We use this to evaluate published <em>in vitro</em> chondrogenesis protocols that use human cell lines, finding variability in cells produced by each. We apply single-nuclear RNA sequencing (snRNA-seq) to our human embryonic stem cell chondrogenesis protocol and perform trajectory alignment with <em>in vivo</em> data to shed light on off-target differentiation <em>in vitro</em>. Using this information, we inhibit FOXO1, a transcription factor active in embryonic osteoblasts and <em>in vitro</em> cells, to increase chondrocyte transcripts <em>in vitro</em>. This work offers a framework for improving <em>in vitro</em> chondrogenesis using developmental data.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"292 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inchworm migration facilitates amoeboid cell adaptation to high-adhesion environments","authors":"Jinqiang Yu, Wenbo Zhou, Dongju Wang, Xiaoting Chao, Taoran Wang, Yuheng Liu, Haozhi Qu, Bingyu Liu, Dong Li, Wei Wang, Hongyu Wang, Huaqing Cai, Li Yu","doi":"10.1016/j.devcel.2025.06.035","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.035","url":null,"abstract":"Cells dynamically adapt their migration modes to environmental conditions, but their response to sticky surfaces, where they risk becoming immobilized, remains unclear. In our study, we discovered that strong adhesion prompts substantial changes in <em>Dictyostelium discoideum</em>, leading to “inchworm migration,” a novel subtype of amoeboid migration. This adaptation involves minimal contact between the cell and the surface, with the cell body standing upright and twisting, followed by rapid reattachment for directed movement. Concurrently, the cells shed migrasomes loaded with negatively charged molecules and adhesion receptors, controlling their adhesion traits to resume pseudopod migration. We identify the repurposing of cytokinesis machinery for migration mode shifting and selective membrane shedding as a crucial mechanism. Neutrophils also exhibit inchworm migration under strong adhesion, suggesting its broader application among amoeboid cells in adapting to high-adhesion environments. Our findings illuminate a programmed, adaptive response in amoeboid cells to navigate effectively through strongly adhesive terrains.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"47 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-07-24DOI: 10.1016/j.devcel.2025.06.037
Sergio Menchero, Christopher Barrington, Clare Critcher, Wazeer Varsally, Gregorio Alanis-Lobato, Kathy K. Niakan, James M.A. Turner
{"title":"Marsupial single-cell transcriptomics identifies temporal diversity in mammalian developmental programs","authors":"Sergio Menchero, Christopher Barrington, Clare Critcher, Wazeer Varsally, Gregorio Alanis-Lobato, Kathy K. Niakan, James M.A. Turner","doi":"10.1016/j.devcel.2025.06.037","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.037","url":null,"abstract":"Single-cell transcriptomics has demonstrated conserved and divergent programs of organogenesis in mammals, but existing studies have focused on eutherians. Marsupials exhibit short gestation and complete development externally, necessitating accelerated differentiation of anterior features required for locomotion and feeding. Hence, they represent a unique outgroup for studying temporal shifts in development, known as heterochrony. Here, we generate a single-cell transcriptomic atlas of gastrulation and early organogenesis in a marsupial, the opossum <em>Monodelphis domestica</em>. We identify previously undocumented tissues undergoing heterochrony and find that transcriptional programs that form anterior structures initiate earlier and progress faster relative to eutherians. The result is uncoupling of transcriptional and morphological timelines, revealing unforeseen diversity in mammalian developmental sequences. Using our transcriptomic dataset, we identified translation as a candidate control mechanism by which anterior prioritization is achieved. Our findings provide insight into the asynchronous progression of developmental programs in marsupials.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"61 6 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-07-23DOI: 10.1016/j.devcel.2025.06.040
Gediminas Greicius, Lorenz Mittermeier, Ruanyi Liang, Kristmundur Sigmundsson, Yarn Kit Chan, Pei-Ju Liao, Alexander Ludwig, David M. Virshup
{"title":"Telocytes deliver essential Wnts directly to murine intestinal stem cells via synapse-like contacts","authors":"Gediminas Greicius, Lorenz Mittermeier, Ruanyi Liang, Kristmundur Sigmundsson, Yarn Kit Chan, Pei-Ju Liao, Alexander Ludwig, David M. Virshup","doi":"10.1016/j.devcel.2025.06.040","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.040","url":null,"abstract":"Spatial and temporal control of Wnt delivery to the intestinal stem cell niche regulates intestinal homeostasis. Telocytes, specialized stromal cells with characteristic long, thin cytoplasmic protrusions, produce essential Wnts for the development and maintenance of this niche. However, how Wnts travel from telocytes to stem cells in the gut remains unclear. Fluorescence and electron microscopy of murine telocytes co-cultured with intestinal organoids identified specialized telocyte extensions that transport and locally secrete Wnts on microvesicles and make intimate contacts with epithelial cells, reminiscent of neuronal contact-based signaling. Investigating the potential role of synapse-forming and plasma membrane-associated platform proteins, we found that depletion of either KANK1 or Liprins from telocytes markedly reduced their filopodia, compromised WNT2 presentation to epithelial cells, and impaired telocyte-dependent organoid growth. Characteristic telocyte structures facilitate Wnt delivery to the intestinal stem cell niche via synapse-like contacts.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"46 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-07-22DOI: 10.1016/j.devcel.2025.06.038
Jo-Wei Allison Hsieh, Pin-Chien Liou, Chia-Chang Lin, Xiufang Dai, Chen-Wei Hu, I-Fan Wang, Jr-Fong Dang, Yi-Chi Ho, Kai-Wen Cheng, Wenjing Xu, Shang-Che Kuo, Chung-Ting Kao, Dian-Xuan Yang, Ray Wang, Ke Xiao, Jeng-Shane Lin, Cheng-Chih Hsu, Chuan-Chih Hsu, Te-Lun Mai, Yuxiang Cheng, Ying-Chung Jimmy Lin
{"title":"Single-cell and spatial multiomics identifies heterogeneous xylem development driven by mechanical stress in Populus","authors":"Jo-Wei Allison Hsieh, Pin-Chien Liou, Chia-Chang Lin, Xiufang Dai, Chen-Wei Hu, I-Fan Wang, Jr-Fong Dang, Yi-Chi Ho, Kai-Wen Cheng, Wenjing Xu, Shang-Che Kuo, Chung-Ting Kao, Dian-Xuan Yang, Ray Wang, Ke Xiao, Jeng-Shane Lin, Cheng-Chih Hsu, Chuan-Chih Hsu, Te-Lun Mai, Yuxiang Cheng, Ying-Chung Jimmy Lin","doi":"10.1016/j.devcel.2025.06.038","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.038","url":null,"abstract":"Xylem, the predominant tissue for structural support, forms tension wood with G-layer-rich fibers under mechanical stress. Despite being recognized over a century ago, three key biological questions remained unclear: (1) are fibers in normal and tension wood distinct cells due to morphological differences? (2) Do tension wood fibers arise from different lineages? (3) What are the key genes controlling tension wood formation? We conducted single-cell RNA sequencing on normal, tension and opposite xylem. Fibers in normal and tension wood belong to the same cell type and lineage. Differential developmental speed and cell-type ratio in tension and opposite xylem were further validated by spatial transcriptomics and metabolomics. Phosphoproteomics showed mechanical sensing mechanisms conserved between stems and roots across angiosperms. We identified a group of genes involved in the cell fate transition in tension wood. The knowledge on the heterogeneity of cell development offers insights into optimizing biomass production and bioenergy yield.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"94 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-07-21DOI: 10.1016/j.devcel.2025.05.012
Filippo Birocchi, Marcela V. Maus
{"title":"Cas12a knockin mice expand the toolbox for in vivo and ex vivo multiplexed genome editing","authors":"Filippo Birocchi, Marcela V. Maus","doi":"10.1016/j.devcel.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.05.012","url":null,"abstract":"Multiplex genome editing is critical for advancing transformative gene therapies and unraveling complex genetic interactions. In a recent issue of <em>Nature Biomedical Engineering</em>, Tang et al. introduced Cas12a knockin mice, providing a versatile platform for disease modeling and the development of multiplexed therapeutic strategies.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"113 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-07-21DOI: 10.1016/j.devcel.2025.06.022
Erica G. Brown, Roddy S. O’Connor
{"title":"T cell InaDAGquacy in the TME driven by phosphoethanolamine","authors":"Erica G. Brown, Roddy S. O’Connor","doi":"10.1016/j.devcel.2025.06.022","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.022","url":null,"abstract":"In a recent issue of <em>Nature Cell Biology</em>, Wang et al. identify phosphoethanolamine as an onco-metabolite that disrupts T cell function through the depletion of diacylglycerol in the Kennedy cycle. These results highlight the substantial role of metabolites in the tumor microenvironment on T cell function.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"303 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental cellPub Date : 2025-07-21DOI: 10.1016/j.devcel.2025.06.036
André B. Medina, Jessica Perochon, Yuanliangzi Tian, Cai T. Johnson, Jack Holcombe, Parvathy Ramesh, Sofia Polcowñuk, Yachuan Yu, Julia B. Cordero
{"title":"Neuroendocrine control of intestinal regeneration through the vascular niche in Drosophila","authors":"André B. Medina, Jessica Perochon, Yuanliangzi Tian, Cai T. Johnson, Jack Holcombe, Parvathy Ramesh, Sofia Polcowñuk, Yachuan Yu, Julia B. Cordero","doi":"10.1016/j.devcel.2025.06.036","DOIUrl":"https://doi.org/10.1016/j.devcel.2025.06.036","url":null,"abstract":"Robust and controlled intestinal regeneration involves reciprocal interactions between the intestinal epithelium and its microenvironment. Here, we identify signaling between enteroendocrine (EE) cells, vasculature-like trachea, and neurons, which drives regional and global stem cell proliferation during adult intestinal regeneration in <em>Drosophila</em>. Reactive oxygen species (ROS) from midgut cells promote production and secretion of diuretic hormone 31 (Dh31), from anterior midgut EE cells. EE and neuronal Dh31 activate tracheal Dh31 receptor, leading to the production of the vascular endothelial growth factor (VEGF)- and platelet-derived-growth-factor (PDGF)-like ligand Pvf1. Pvf1 induces tracheal remodeling and intestinal stem cell (ISC) proliferation through autocrine and paracrine Pvr/mitogen-activated protein kinase (MAPK) signaling, respectively. While EE Dh31 exerts broad control of ISC proliferation throughout the midgut, effects of the neuronal source of the ligand appear restricted to the posterior midgut. Collectively, our work discovered an EE/neuronal/vascular signaling network, controlling global and domain-specific ISC proliferation during adult intestinal regeneration.","PeriodicalId":11157,"journal":{"name":"Developmental cell","volume":"282 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}