PUBLICATION
Cardiomyocyte heterogeneity during zebrafish development and regeneration
- Authors
- Tsedeke, A.T., Allanki, S., Gentile, A., Jimenez-Amilburu, V., Rasouli, S.J., Guenther, S., Lai, S.L., Stainier, D.Y.R., Marín-Juez, R.
- ID
- ZDB-PUB-210416-9
- Date
- 2021
- Source
- Developmental Biology 476: 259-271 (Journal)
- Registered Authors
- Lai, Shih-Lei (Ben), Marín-Juez, Rubén, Stainier, Didier
- Keywords
- Cardiomyocyte heterogeneity, Cardiomyocyte maturation, Heart development, Heart regeneration, Zebrafish
- Datasets
- GEO:GSE157662
- MeSH Terms
-
- Animals
- Cell Proliferation
- Heart/embryology*
- Heart Ventricles/metabolism
- Myocardium/metabolism
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/metabolism*
- Regeneration/physiology*
- Signal Transduction
- Zebrafish/embryology
- Zebrafish Proteins/genetics
- PubMed
- 33857482 Full text @ Dev. Biol.
Citation
Tsedeke, A.T., Allanki, S., Gentile, A., Jimenez-Amilburu, V., Rasouli, S.J., Guenther, S., Lai, S.L., Stainier, D.Y.R., Marín-Juez, R. (2021) Cardiomyocyte heterogeneity during zebrafish development and regeneration. Developmental Biology. 476:259-271.
Abstract
Contrary to adult mammals, zebrafish are able to regenerate their heart after cardiac injury. This regenerative response relies, in part, on the endogenous ability of cardiomyocytes (CMs) to dedifferentiate and proliferate to replenish the lost muscle. However, CM heterogeneity and population dynamics during development and regeneration require further investigation. Through comparative transcriptomic analyses of the developing and adult zebrafish heart, we identified tnnc2 and tnni4b.3 expression as markers for CMs at early and late developmental stages, respectively. Using newly developed reporter lines for these genes, we investigated their expression dynamics during heart development and regeneration. tnnc2 reporter lines label most CMs at embryonic stages, and this labeling declines rapidly during larval stages; in adult hearts, tnnc2 reporter expression is only detectable in a small subset of CMs. Conversely, expression of a tnni4b.3 reporter is initially visible in CMs in the outer curvature of the ventricle at larval stages, and it is subsequently present in a vast majority of the CMs in adult hearts. To further characterize the adult CMs labeled by the tnnc2 (i.e., embryonic) reporter, we performed transcriptomic analysis and found that they express markers of immature CMs as well as genes encoding components of the Notch signaling pathway. In support of this finding, we observed, using two different reporters, that these CMs display higher levels of Notch signaling. Moreover, during adult heart regeneration, CMs in the injured area activate the embryonic CM reporter and downregulate the tnni4b.3 reporter, further highlighting the molecular changes in regenerating CMs. Overall, our findings provide additional evidence for cardiomyocyte heterogeneity in adult zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping