Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous System

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-Coding RNA Pub Date : 2023-12-22 DOI:10.3390/ncrna10010001

Christopher Pai, Rajarshi Sengupta, R. Heuckeroth

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引用次数: 0

Abstract

The enteric nervous system (ENS) is an essential network of neurons and glia in the bowel wall. Defects in ENS development can result in Hirschsprung disease (HSCR), a life-threatening condition characterized by severe constipation, abdominal distention, bilious vomiting, and failure to thrive. A growing body of literature connects HSCR to alterations in miRNA expression, but there are limited data on the normal miRNA landscape in the developing ENS. We sequenced small RNAs (smRNA-seq) and messenger RNAs (mRNA-seq) from ENS precursor cells of mid-gestation Ednrb-EGFP mice and compared them to aggregated RNA from all other cells in the developing bowel. Our smRNA-seq results identified 73 miRNAs that were significantly enriched and highly expressed in the developing ENS, with miR-9, miR-27b, miR-124, miR-137, and miR-488 as our top 5 miRNAs that are conserved in humans. However, contrary to prior reports, our follow-up analyses of miR-137 showed that loss of Mir137 in Nestin-cre, Wnt1-cre, Sox10-cre, or Baf53b-cre lineage cells had no effect on mouse survival or ENS development. Our data provide important context for future studies of miRNAs in HSCR and other ENS diseases and highlight open questions about facility-specific factors in development.

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测序揭示发育中小鼠肠神经系统中丰富的 miRNAs

肠神经系统（ENS）是肠壁神经元和胶质细胞的重要网络。肠神经系统的发育缺陷可导致赫氏肠病（HSCR），这是一种以严重便秘、腹胀、胆汁性呕吐和无法茁壮成长为特征的危及生命的疾病。越来越多的文献将 HSCR 与 miRNA 表达的改变联系起来，但有关发育中耳鼻咽喉神经系统正常 miRNA 状况的数据却很有限。我们对妊娠中期Ednrb-EGFP小鼠ENS前体细胞的小RNA（smRNA-seq）和信使RNA（mRNA-seq）进行了测序，并将它们与发育中肠道所有其他细胞的RNA聚集进行了比较。我们的smRNA-seq结果发现，73个miRNA在发育中的ENS中显著富集并高表达，其中miR-9、miR-27b、miR-124、miR-137和miR-488是我们发现的在人类中保守的前5个miRNA。然而，与之前的报道相反，我们对 miR-137 的后续分析表明，Nestin-cre、Wnt1-cre、Sox10-cre 或 Baf53b-cre 系细胞中 Mir137 的缺失对小鼠的存活或耳鼻咽喉发育没有影响。我们的数据为今后研究 HSCR 和其他耳鼻咽喉疾病中的 miRNA 提供了重要的背景，并突出了发育过程中设施特异性因素的未决问题。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

6.70

自引率

4.70%

发文量

审稿时长

10 weeks

期刊介绍： Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.