PUBLICATION
Krüppel-like factor 1 is a core cardiomyogenic trigger in zebrafish
- Authors
- Ogawa, M., Geng, F.S., Humphreys, D.T., Kristianto, E., Sheng, D.Z., Hui, S.P., Zhang, Y., Sugimoto, K., Nakayama, M., Zheng, D., Hesselson, D., Hodson, M.P., Bogdanovic, O., Kikuchi, K.
- ID
- ZDB-PUB-210410-4
- Date
- 2021
- Source
- Science (New York, N.Y.) 372: 201-205 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cardiomegaly, Exercise-Induced
- Cell Dedifferentiation
- Cell Differentiation
- Cell Proliferation
- Cellular Reprogramming*
- Gene Expression Regulation
- Gene Regulatory Networks
- Glycolysis
- Heart/embryology
- Heart/physiology*
- Heart Ventricles/cytology
- Kruppel-Like Transcription Factors/genetics
- Kruppel-Like Transcription Factors/metabolism*
- Muscle Development
- Myocardium/metabolism
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/physiology*
- Pentose Phosphate Pathway
- Regeneration*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 33833125 Full text @ Science
Citation
Ogawa, M., Geng, F.S., Humphreys, D.T., Kristianto, E., Sheng, D.Z., Hui, S.P., Zhang, Y., Sugimoto, K., Nakayama, M., Zheng, D., Hesselson, D., Hodson, M.P., Bogdanovic, O., Kikuchi, K. (2021) Krüppel-like factor 1 is a core cardiomyogenic trigger in zebrafish. Science (New York, N.Y.). 372:201-205.
Abstract
Cardiac regeneration requires dedifferentiation and proliferation of mature cardiomyocytes, but the mechanisms underlying this plasticity remain unclear. Here, we identify a potent cardiomyogenic role for Krüppel-like factor 1 (Klf1/Eklf), which is induced in adult zebrafish myocardium upon injury. Myocardial inhibition of Klf1 function does not affect heart development, but it severely impairs regeneration. Transient Klf1 activation is sufficient to expand mature myocardium in uninjured hearts. Klf1 directs epigenetic reprogramming of the cardiac transcription factor network, permitting coordinated cardiomyocyte dedifferentiation and proliferation. Myocardial expansion is supported by Klf1-induced rewiring of mitochondrial metabolism from oxidative respiration to anabolic pathways. Our findings establish Klf1 as a core transcriptional regulator of cardiomyocyte renewal in adult zebrafish hearts.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping