PUBLICATION
HOPX-associated molecular programs control cardiomyocyte cell states underpinning cardiac structure and function
- Authors
- Friedman, C.E., Cheetham, S.W., Negi, S., Mills, R.J., Ogawa, M., Redd, M.A., Chiu, H.S., Shen, S., Sun, Y., Mizikovsky, D., Bouveret, R., Chen, X., Voges, H.K., Paterson, S., De Angelis, J.E., Andersen, S.B., Cao, Y., Wu, Y., Jafrani, Y.M.A., Yoon, S., Faulkner, G.J., Smith, K.A., Porrello, E., Harvey, R.P., Hogan, B.M., Nguyen, Q., Zeng, J., Kikuchi, K., Hudson, J.E., Palpant, N.J.
- ID
- ZDB-PUB-231214-9
- Date
- 2023
- Source
- Developmental Cell 59(1): 91-107.e6 (Journal)
- Registered Authors
- De Angelis, Jessica, Hogan, Ben M., Paterson, Scott, Smith, Kelly
- Keywords
- CRISPRi, DamID, cardiomyocyte physiology, cell proliferation, complex traits, heart development, human-induced pluripotent stem cell, maturation, regeneration, zebrafish cardiac regeneration
- MeSH Terms
-
- Animals
- Cell Differentiation/genetics
- Cell Proliferation
- Homeodomain Proteins/genetics
- Homeodomain Proteins/metabolism
- Humans
- Induced Pluripotent Stem Cells*
- Myocytes, Cardiac*/metabolism
- Zebrafish/metabolism
- PubMed
- 38091997 Full text @ Dev. Cell
Citation
Friedman, C.E., Cheetham, S.W., Negi, S., Mills, R.J., Ogawa, M., Redd, M.A., Chiu, H.S., Shen, S., Sun, Y., Mizikovsky, D., Bouveret, R., Chen, X., Voges, H.K., Paterson, S., De Angelis, J.E., Andersen, S.B., Cao, Y., Wu, Y., Jafrani, Y.M.A., Yoon, S., Faulkner, G.J., Smith, K.A., Porrello, E., Harvey, R.P., Hogan, B.M., Nguyen, Q., Zeng, J., Kikuchi, K., Hudson, J.E., Palpant, N.J. (2023) HOPX-associated molecular programs control cardiomyocyte cell states underpinning cardiac structure and function. Developmental Cell. 59(1):91-107.e6.
Abstract
Genomic regulation of cardiomyocyte differentiation is central to heart development and function. This study uses genetic loss-of-function human-induced pluripotent stem cell-derived cardiomyocytes to evaluate the genomic regulatory basis of the non-DNA-binding homeodomain protein HOPX. We show that HOPX interacts with and controls cardiac genes and enhancer networks associated with diverse aspects of heart development. Using perturbation studies in vitro, we define how upstream cell growth and proliferation control HOPX transcription to regulate cardiac gene programs. We then use cell, organoid, and zebrafish regeneration models to demonstrate that HOPX-regulated gene programs control cardiomyocyte function in development and disease. Collectively, this study mechanistically links cell signaling pathways as upstream regulators of HOPX transcription to control gene programs underpinning cardiomyocyte identity and function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping