期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-29311-7
关键词
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资金
- Swiss National Science Foundation [PP00P3_139093]
- SNSF R'Equip grant [316030_150838]
- SNSF [CRSII5_180345, 320030_182690, 310030L_182575, 310030_175841, CRSII5_177208, P400PB_191057]
- Marie Curie Career Integration Grant from the European Commission [CIG PCIG14-GA-2013-631984]
- Canton of Zurich
- Swiss Heart Foundation
- ZUNIV FAN/UZH Alumni
- University of Colorado School of Medicine, Department of Pediatrics and Section of Developmental Biology
- Helen and Arthur E. Johnson Foundation
- Children's Hospital Colorado Foundation
- Swiss Bridge Foundation
- EuFishBioMed
- ERC Starting Grant [2013 337703]
- Human Frontier Science Program (HFSP) long-term postdoctoral fellowship [LT000078/2016]
- Stiftung fur Angewandte Krebsforschung
- University of Zurich's Research Priority Program Evolution in Action
- UZH CanDoc
- Company of Biologists
- UZH Foundation for Research in Science and the Humanities
- Swiss National Science Foundation (SNF) [310030_175841, 316030_150838, 310030L_182575, CRSII5_180345, P400PB_191057, PP00P3_139093] Funding Source: Swiss National Science Foundation (SNF)
This study uncovers the early origins of mesothelium progenitor cells in zebrafish, linking the function of the Hand2 gene to mesothelium formation and the re-activation of mesothelioma tumors.
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. The mesothelium supports homeostasis and regeneration, yet its development origins remain unclear. Here, the authors uncovered the earliest mesothelium progenitor cells in zebrafish, linking Hand2 gene function to mesothelium formation and its re-activation to mesothelioma tumors.
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