Rodrigo Moreno-Campos, Nikhita S. Mummaneni, Rosa A. Uribe
{"title":"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","authors":"Rodrigo Moreno-Campos, Nikhita S. Mummaneni, Rosa A. Uribe","doi":"10.1096/fj.202501470R","DOIUrl":null,"url":null,"abstract":"<p>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 <i>hoxb5b</i>, <i>hoxa4a</i>, <i>etv1,</i> and <i>ret,</i> 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.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 17","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202501470R","citationCount":"0","resultStr":"{\"title\":\"Whole-Gut Spatial Genomic Analysis Reveals Molecular Regionalization of the Differentiating Zebrafish Enteric Nervous System\",\"authors\":\"Rodrigo Moreno-Campos, Nikhita S. Mummaneni, Rosa A. 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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 <i>hoxb5b</i>, <i>hoxa4a</i>, <i>etv1,</i> and <i>ret,</i> 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.</p>\",\"PeriodicalId\":50455,\"journal\":{\"name\":\"The FASEB Journal\",\"volume\":\"39 17\",\"pages\":\"\"},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2025-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202501470R\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The FASEB Journal\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202501470R\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The FASEB Journal","FirstCategoryId":"99","ListUrlMain":"https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202501470R","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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.