Prummel, Karin D; Crowell, Helena L; Nieuwenhuize, Susan; Brombacher, Eline C; Daetwyler, Stephan; Soneson, Charlotte; Kresoja-Rakic, Jelena; Kocere, Agnese; Ronner, Manuel; Ernst, Alexander; Labbaf, Zahra; Clouthier, David E; Firulli, Anthony B; Sánchez-Iranzo, Héctor; Naganathan, Sundar R; O'Rourke, Rebecca; Raz, Erez; Mercader, Nadia; Burger, Alexa; Felley-Bosco, Emanuela; ... (2022). Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma. Nature Communications, 13(1), p. 1677. Springer Nature 10.1038/s41467-022-29311-7
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The mesothelium lines body cavities and surrounds internal organs, widely contributing to homeostasis and regeneration. Mesothelium disruptions cause visceral anomalies and mesothelioma tumors. Nonetheless, the embryonic emergence of mesothelia remains incompletely understood. Here, we track mesothelial origins in the lateral plate mesoderm (LPM) using zebrafish. Single-cell transcriptomics uncovers a post-gastrulation gene expression signature centered on hand2 in distinct LPM progenitor cells. We map mesothelial progenitors to lateral-most, hand2-expressing LPM and confirm conservation in mouse. Time-lapse imaging of zebrafish hand2 reporter embryos captures mesothelium formation including pericardium, visceral, and parietal peritoneum. We find primordial germ cells migrate with the forming mesothelium as ventral migration boundary. Functionally, hand2 loss disrupts mesothelium formation with reduced progenitor cells and perturbed migration. In mouse and human mesothelioma, we document expression of LPM-associated transcription factors including Hand2, suggesting re-initiation of a developmental program. Our data connects mesothelium development to Hand2, expanding our understanding of mesothelial pathologies.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy |
UniBE Contributor: |
Ernst, Alexander Uwe Johann, Mercader Huber, Nadia Isabel |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Springer Nature |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
01 Apr 2022 10:40 |
Last Modified: |
05 Dec 2022 16:18 |
Publisher DOI: |
10.1038/s41467-022-29311-7 |
PubMed ID: |
35354817 |
BORIS DOI: |
10.48350/168857 |
URI: |
https://boris.unibe.ch/id/eprint/168857 |
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