Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous System

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 gr...

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Päätekijät: Christopher Pai, Rajarshi Sengupta, Robert O. Heuckeroth
Aineistotyyppi: Artikkeli
Kieli:English
Julkaistu: MDPI AG 2023-12-01
Sarja:Non-Coding RNA
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Linkit:https://www.mdpi.com/2311-553X/10/1/1
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author Christopher Pai
Rajarshi Sengupta
Robert O. Heuckeroth
author_facet Christopher Pai
Rajarshi Sengupta
Robert O. Heuckeroth
author_sort Christopher Pai
collection DOAJ
description 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 <i>Ednrb-EGFP</i> 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 <i>Mir137</i> in <i>Nestin-cre</i>, <i>Wnt1-cre</i>, <i>Sox10-cre</i>, or <i>Baf53b-cre</i> 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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spelling doaj.art-da9cd0ceb1ea498bbfc508146a21f0af2024-02-23T15:29:34ZengMDPI AGNon-Coding RNA2311-553X2023-12-01101110.3390/ncrna10010001Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous SystemChristopher Pai0Rajarshi Sengupta1Robert O. Heuckeroth2The Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USAAmerican Association for Cancer Research, Philadelphia, PA 19106, USAThe Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USAThe 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 <i>Ednrb-EGFP</i> 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 <i>Mir137</i> in <i>Nestin-cre</i>, <i>Wnt1-cre</i>, <i>Sox10-cre</i>, or <i>Baf53b-cre</i> 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.https://www.mdpi.com/2311-553X/10/1/1enteric nervous systemHirschsprung diseasemiR-9miR-27bmiR-124miR-137
spellingShingle Christopher Pai
Rajarshi Sengupta
Robert O. Heuckeroth
Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous System
Non-Coding RNA
enteric nervous system
Hirschsprung disease
miR-9
miR-27b
miR-124
miR-137
title Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous System
title_full Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous System
title_fullStr Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous System
title_full_unstemmed Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous System
title_short Sequencing Reveals miRNAs Enriched in the Developing Mouse Enteric Nervous System
title_sort sequencing reveals mirnas enriched in the developing mouse enteric nervous system
topic enteric nervous system
Hirschsprung disease
miR-9
miR-27b
miR-124
miR-137
url https://www.mdpi.com/2311-553X/10/1/1
work_keys_str_mv AT christopherpai sequencingrevealsmirnasenrichedinthedevelopingmouseentericnervoussystem
AT rajarshisengupta sequencingrevealsmirnasenrichedinthedevelopingmouseentericnervoussystem
AT robertoheuckeroth sequencingrevealsmirnasenrichedinthedevelopingmouseentericnervoussystem