全肠道空间基因组分析揭示分化的斑马鱼肠神经系统的分子区域化

IF 4.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Rodrigo Moreno-Campos, Nikhita S. Mummaneni, Rosa A. Uribe
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引用次数: 0

摘要

肠神经系统(ENS)是肠道的内在神经系统,控制肠道运动、肠道屏障功能和水分平衡等基本功能。ENS在肠道和控制肠道稳态所需的特定转录状态的背景下显示复杂的3D结构。在发育过程中,ENS由肠神经祖细胞(ENPs)发展而来,这些细胞迁移到肠道并分化成功能多样的神经元类型。不正确的ENS发育会破坏ENS功能并诱发各种肠道疾病,包括先天性先天性巨结肠病或各种其他功能性肠道神经疾病,如食道失弛弛症。在这项研究中,我们使用斑马鱼幼虫模型,在细胞分辨率下对分化ENS进行了全肠道空间基因组分析(SGA)。为此,研究人员开发了一个整合早期和晚期ENS发育阶段的管道,通过连接各种空间和转录维度来发现区域化细胞群及其共表达相似性。我们确定了肠道周围完整ENS的3D网络,并根据分期预测了细胞连接特性。空间可变基因,如hoxb5b、hoxa4a、etv1和ret,沿着肠道轴被区域化,表明它们可能对ENS的发展具有精确的时空控制。SGA在ENS开发中的应用为其细胞转录网络和相互作用提供了新的见解,并提供了基线数据集,以进一步推进我们对肠道神经发育障碍(如巨结肠病和先天性肠神经病变)的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Whole-Gut Spatial Genomic Analysis Reveals Molecular Regionalization of the Differentiating Zebrafish Enteric Nervous System

Whole-Gut Spatial Genomic Analysis Reveals Molecular Regionalization of the Differentiating Zebrafish Enteric Nervous System

Whole-Gut Spatial Genomic Analysis Reveals Molecular Regionalization of the Differentiating Zebrafish Enteric Nervous System

Whole-Gut Spatial Genomic Analysis Reveals Molecular Regionalization of the Differentiating Zebrafish Enteric Nervous System

The enteric nervous system (ENS) is the intrinsic nervous system of the gut and controls essential functions, such as gut motility, intestinal barrier function, and water balance. The ENS displays a complex 3D architecture within the context of the gut and specific transcriptional states needed to control gut homeostasis. During development, the ENS develops from enteric neural progenitor cells (ENPs) that migrate into the gut and differentiate into functionally diverse neuron types. Incorrect ENS development can disrupt ENS function and induce various gut disorders, including the congenital disease Hirschsprung disease, or various other functional gut neurological disorders, such as esophageal achalasia. In this study, we used the zebrafish larval model and performed whole gut spatial genomic analysis (SGA) of the differentiating ENS at cellular resolution. To that end, a pipeline was developed that integrated early and late developmental ENS stages by linking various spatial and transcriptional dimensions to discover regionalized cellular groups and their co-expression similarity. We identified 3D networks of intact ENS surrounding the gut and predicted cellular connectivity properties based on the stage. Spatial variable genes, such as hoxb5b, hoxa4a, etv1, and ret, were regionalized along gut axes, suggesting they may have a precise spatiotemporal control of ENS development. The application of SGA to ENS development provides new insights into its cellular transcriptional networks and interactions and provides a baseline data set to further advance our understanding of gut neurodevelopmental disorders such as Hirschsprung disease and congenital enteric neuropathies.

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来源期刊
The FASEB Journal
The FASEB Journal 生物-生化与分子生物学
CiteScore
9.20
自引率
2.10%
发文量
6243
审稿时长
3 months
期刊介绍: The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
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