PUBLICATION
Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma
- Authors
- Prummel, K.D., Crowell, H.L., Nieuwenhuize, S., Brombacher, E.C., Daetwyler, S., Soneson, C., Kresoja-Rakic, J., Kocere, A., Ronner, M., Ernst, A., Labbaf, Z., Clouthier, D.E., Firulli, A.B., Sánchez-Iranzo, H., Naganathan, S.R., O'Rourke, R., Raz, E., Mercader, N., Burger, A., Felley-Bosco, E., Huisken, J., Robinson, M.D., Mosimann, C.
- ID
- ZDB-PUB-220401-2
- Date
- 2022
- Source
- Nature communications 13: 1677 (Journal)
- Registered Authors
- Burger, Alexa, Clouthier, David, Huisken, Jan, Kocere, Agnese, Labbaf, Zahra, Mercader Huber, Nadia, Mosimann, Christian, Naganathan, Sundar, Nieuwenhuize, Susan, Prummel, Karin, Raz, Erez
- Keywords
- none
- MeSH Terms
-
- Animals
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/metabolism
- Epithelium/metabolism
- Mesothelioma*/genetics
- Mice
- Transcription Factors/metabolism
- Zebrafish*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 35354817 Full text @ Nat. Commun.
Citation
Prummel, K.D., Crowell, H.L., Nieuwenhuize, S., Brombacher, E.C., Daetwyler, S., Soneson, C., Kresoja-Rakic, J., Kocere, A., Ronner, M., Ernst, A., Labbaf, Z., Clouthier, D.E., Firulli, A.B., Sánchez-Iranzo, H., Naganathan, S.R., O'Rourke, R., Raz, E., Mercader, N., Burger, A., Felley-Bosco, E., Huisken, J., Robinson, M.D., Mosimann, C. (2022) Hand2 delineates mesothelium progenitors and is reactivated in mesothelioma. Nature communications. 13:1677.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping