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识别指令通路,指定移动肠神经细胞的子集在鼠标胚胎的波浪前沿的信号通路

Bingyan Zhou¹, Chenzhao Feng², Song Sun³

¹Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Hubei Clinical Center of Hirschsprung's Disease and Allied Disorders, Wuhan, Hubei 430030, China.

Developmental cell

|April 18, 2024

概括

开创性肠道神经细胞 (ENCCs) 引导肠道发育. 这项研究绘制了它们的旅程图,揭示了特异性和相互作用的分子线索,这对于理解肠道神经系统疾病至关重要.

科学领域:

发育生物学是发展生物学.
神经科学是一个神经科学.
遗传学是一个遗传学.

背景情况:

肠道神经系统 (ENS) 的发育依赖于肠道神经细胞 (ENCCs) 来进行肠道殖民.
规范ENCC规范和利基互动的分子机制尚不完全理解.

研究的目的:

在小鼠胚胎发育过程中绘制波ENCCs的时空动态和分子景观.
为了确定ENCC规范,差异化和肠道微环境相互作用的分子调节者.
将已识别的途径与人体内神经系统 (ENS) 缺陷,如赫施普朗格病 (Hirschsprung) 联系起来.

主要方法:

单细胞RNA测序的一个细胞.
空间转录组学空间转录组学
对小鼠胚胎发育的分析.
检查人类的赫施普朗格病肠道组织.

主要成果:

在迁移过程中,波浪前ENCC的功效逐渐下降.
确定了介导ENCC-利基互动的关键转录因子和信号通路 (ephrin-Eph,Wnt-Frizzled,Sema3a-Nrp1).这些关键转录因子和信号通路被确定.
这些通路的干扰与人体内神经系统的形有关.
在肠道中,ENCC的到来会诱导特定区域和细胞类型的转录性变化.

结论:

本研究提供了在单细胞水平上对ENS发展的全面路线图.
已识别的分子机制和途径对于正常的ENS形成和肠道微环境发展至关重要.
这些发现提供了对肠神经系统疾病的病原体和潜在治疗点的见解.

关键词:

赫什斯普朗格病 (Hirschsprung's disease) 是一种疾病.肠道神经系统肠道神经系统肠道神经细胞肠道神经细胞单细胞转录组学单细胞转录组学空间转录学空间转录学

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