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β-Catenin drives distinct transcriptional networks in proliferative and nonproliferative cardiomyocytes
- Source :
- Development (Cambridge, England). 147(22)
- Publication Year :
- 2020
-
Abstract
- The inability of the adult mammalian heart to regenerate represents a fundamental barrier in heart failure management. In contrast, the neonatal heart retains a transient regenerative capacity, but the underlying mechanisms for the developmental loss of cardiac regenerative capacity in mammals are not fully understood. Wnt/β-catenin signaling has been proposed as a key cardio-regenerative pathway driving cardiomyocyte proliferation. Here, we show that Wnt/β-catenin signaling potentiates neonatal mouse cardiomyocyte proliferation in vivo and immature human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) proliferation in vitro. In contrast, Wnt/β-catenin signaling in adult mice is cardioprotective but fails to induce cardiomyocyte proliferation. Transcriptional profiling and chromatin immunoprecipitation sequencing of neonatal mouse and hPSC-CM revealed a core Wnt/β-catenin-dependent transcriptional network governing cardiomyocyte proliferation. In contrast, β-catenin failed to re-engage this neonatal proliferative gene network in the adult heart despite partial transcriptional re-activation of a neonatal glycolytic gene program. These findings suggest that β-catenin may be repurposed from regenerative to protective functions in the adult heart in a developmental process dependent on the metabolic status of cardiomyocytes.
- Subjects :
- Beta-catenin
Transcription, Genetic
Induced Pluripotent Stem Cells
Regenerative medicine
03 medical and health sciences
Mice
0302 clinical medicine
Transcriptional regulation
Myocyte
Animals
Humans
Gene Regulatory Networks
Myocytes, Cardiac
Induced pluripotent stem cell
Molecular Biology
Wnt Signaling Pathway
beta Catenin
030304 developmental biology
Cell Proliferation
0303 health sciences
biology
Wnt signaling pathway
Cell biology
Catenin
biology.protein
Developmental biology
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 14779129
- Volume :
- 147
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- Development (Cambridge, England)
- Accession number :
- edsair.doi.dedup.....732e89c3dc2e3811a65e2e7b238f3dee