A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia.
A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia.
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DOI：
10.1038/s41467-023-41492-3
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发表时间：
2023-09-22
影响因子：
16.6
通讯作者：
Pachnis, Vassilis
中科院分区：
文献类型：
--
作者：
Laddach, Anna;Chng, Song Hui;Lasrado, Reena;Progatzky, Franze;Shapiro, Michael;Erickson, Alek;Castaneda, Marisol Sampedro;Artemov, Artem V.;Bon-Frauches, Ana Carina;Amaniti, Eleni-Maria;Kleinjung, Jens;Boeing, Stefan;Ultanir, Sila;Adameyko, Igor;Pachnis, Vassilis
神经胶质细胞被认为是神经前体细胞的来源，但支持成体神经胶质细胞神经发生潜能的机制尚不清楚。使用单细胞转录组学分析，我们表明，肠神经胶质细胞代表自主神经嵴细胞达到的细胞状态，因为它们沿沿着线性分化轨迹过渡，使它们能够保留神经原性潜力，同时获得成熟的神经胶质功能。早期肠神经系统祖细胞中的关键神经源性位点在成熟的肠胶质细胞中保持开放的染色质构型，从而在适当的条件下促进神经元分化。在肠神经发生的细胞培养模型和肠损伤模型中肠神经胶质细胞的分子分析和基因靶向表明，神经胶质细胞的神经元分化是由早期祖细胞体内采用的转录程序驱动的。我们的工作提供了对支撑肠神经回路发展的监管格局的机制性见解，并为推进神经胶质细胞作为治疗神经缺陷的治疗剂提供了平台。肠神经系统包括调节胃肠功能的肠内神经胶质网络。基于单细胞分析，作者提出了一个模型，其中神经源性分化路径分支从胶质轨迹。
Glial cells have been proposed as a source of neural progenitors, but the mechanisms underpinning the neurogenic potential of adult glia are not known. Using single cell transcriptomic profiling, we show that enteric glial cells represent a cell state attained by autonomic neural crest cells as they transition along a linear differentiation trajectory that allows them to retain neurogenic potential while acquiring mature glial functions. Key neurogenic loci in early enteric nervous system progenitors remain in open chromatin configuration in mature enteric glia, thus facilitating neuronal differentiation under appropriate conditions. Molecular profiling and gene targeting of enteric glial cells in a cell culture model of enteric neurogenesis and a gut injury model demonstrate that neuronal differentiation of glia is driven by transcriptional programs employed in vivo by early progenitors. Our work provides mechanistic insight into the regulatory landscape underpinning the development of intestinal neural circuits and generates a platform for advancing glial cells as therapeutic agents for the treatment of neural deficits. The enteric nervous system encompasses the gut-intrinsic neuroglial networks that regulate gastrointestinal functions. Based on single-cell analysis, the authors propose a model in which neurogenic differentiation paths branch from a gliogenic trajectory.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
4.2
作者：
Eidam, Hilary Schenck;Russell, John;Cheung, Mui
通讯作者：
Cheung, Mui
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作者：
Delile, Julien;Rayon, Teresa;Sagner, Andreas
通讯作者：
Sagner, Andreas
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作者：
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通讯作者：
Alquier, Thierry
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2.7
作者：
Bondurand, Nadege;Sham, Mai Har
通讯作者：
Sham, Mai Har