Heterogeneity and Phenotypic Plasticity of Glial Cells in the Mammalian Enteric Nervous System
Heterogeneity and Phenotypic Plasticity of Glial Cells in the Mammalian Enteric Nervous System
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DOI：
10.1002/glia.22746
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发表时间：
2015-02-01
期刊：
影响因子：
6.2
通讯作者：
Pachnis, Vassilis
中科院分区：
文献类型：
--
作者：
Boesmans, Werend;Lasrado, Reena;Pachnis, Vassilis
肠神经胶质细胞对于肠神经系统胃肠道稳态的自主控制至关重要。肠胶质细胞具有多种不同的功能，但这些功能是否由具有独特表型和功能的特殊亚型执行仍然难以捉摸。我们使用双标记马赛克分析和诱导谱系追踪来表征肌间神经丛中肠 GLIA 的形态和动态分子标记表达。通过 Ca2+ 成像对单独识别的肠神经胶质细胞进行功能分析。我们的实验已经鉴定出成年小鼠胃肠道中四种形态不同的肠胶质细胞亚群。标记表达分析显示，肌间神经丛中的大多数胶质细胞共表达胶质纤维酸性蛋白（GFAP）、S100 和 Sox10。然而，肌间神经节外的相当一部分（高达 80%）的神经胶质细胞没有标记这些标记。谱系追踪实验表明，这些标记的替代组合反映了动态基因调控而不是谱系限制。在功能水平上，三种肌间神经胶质细胞亚型可以通过它们对三磷酸腺苷的不同反应来区分。总之，我们的研究揭示了肠胶质细胞的广泛异质性和表型可塑性，并为进一步研究奠定了框架，旨在破译它们在消化功能和疾病中的作用。 GLIA 2015；63:229-241
Enteric glial cells are vital for the autonomic control of gastrointestinal homeostasis by the enteric nervous system. Several different functions have been assigned to enteric glial cells but whether these are performed by specialized subtypes with a distinctive phenotype and function remains elusive. We used Mosaic Analysis with Double Markers and inducible lineage tracing to characterize the morphology and dynamic molecular marker expression of enteric GLIA in the myenteric plexus. Functional analysis in individually identified enteric glia was performed by Ca2+ imaging. Our experiments have identified four morphologically distinct subpopulations of enteric glia in the gastrointestinal tract of adult mice. Marker expression analysis showed that the majority of glia in the myenteric plexus co-express glial fibrillary acidic protein (GFAP), S100, and Sox10. However, a considerable fraction (up to 80%) of glia outside the myenteric ganglia, did not label for these markers. Lineage tracing experiments suggest that these alternative combinations of markers reflect dynamic gene regulation rather than lineage restrictions. At the functional level, the three myenteric glia subtypes can be distinguished by their differential response to adenosine triphosphate. Together, our studies reveal extensive heterogeneity and phenotypic plasticity of enteric glial cells and set a framework for further investigations aimed at deciphering their role in digestive function and disease. GLIA 2015;63:229-241