A branching model of cell fate decisions in the enteric nervous system
A branching model of cell fate decisions in the enteric nervous system
Abstract How neurogenesis and gliogenesis are coordinated during development and why mature glial cells often share properties with neuroectodermal progenitors remains unclear. Here, we have used single cell RNA sequencing to map the regulatory landscape of neuronal and glial differentiation in the mammalian enteric nervous system (ENS). Our analysis indicates that neurogenic trajectories branch directly from a linear gliogenic axis defined by autonomic neural crest cells adopting sequential states as they progressively lose their strong neurogenic bias and acquire properties of adult enteric glia. We identify gene modules associated with transcriptional programs driving enteric neurogenesis and cell state transitions along the gliogenic axis. By comparing the chromatin accessibility profile of autonomic neural crest and adult enteric glia we provide evidence that the latter maintain an epigenetic memory of their neurogenic past. Finally, we demonstrate that adult enteric glia maintain neurogenic potential and are capable of generating enteric neurons in certain contexts by activating transcriptional programs employed by early ENS progenitors. Our studies uncover a novel configuration of enteric neurogenesis and gliogenesis that enables the coordinate development of ENS lineages and provides a mechanistic explanation for the ability of enteric glia to be functionally integrated into the adult intestine and simultaneously maintain attributes of early ENS progenitors.
Pachnis Vassilis、Chng Song Hui、Lasrado Reena、Artemov Artem、Castaneda Marisol Sampedro、Boeing Stefan、Shapiro Michael、Laddach Anna、Progatzky Fr?nze、Kleinjung Jens、Ultanir Sila、Erickson Alek、Adameyko Igor、Bon-Frauches Ana Carina
Nervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteDepartment of Neuroimmunology, Center for Brain Research, Medical University of ViennaKinases and Brain Development Laboratory, the Francis Crick InstituteBioinformatics and Biostatistics Science Technology Platform, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick InstituteKinases and Brain Development Laboratory, the Francis Crick InstituteDepartment of Physiology and Pharmacology, Karolinska InstitutetDepartment of Neuroimmunology, Center for Brain Research, Medical University of Vienna||Kinases and Brain Development Laboratory, the Francis Crick InstituteNervous System Development and Homeostasis Laboratory, the Francis Crick Institute
细胞生物学分子生物学遗传学
Pachnis Vassilis,Chng Song Hui,Lasrado Reena,Artemov Artem,Castaneda Marisol Sampedro,Boeing Stefan,Shapiro Michael,Laddach Anna,Progatzky Fr?nze,Kleinjung Jens,Ultanir Sila,Erickson Alek,Adameyko Igor,Bon-Frauches Ana Carina.A branching model of cell fate decisions in the enteric nervous system[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2022.07.12.499640.点此复制
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