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Updated: Nov 1, 2025
Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
Published on: February 12, 2021
p53 Promotes Differentiation of Cardiomyocytes from hiPSC through Wnt Signaling-Mediated Mesendodermal
Yuanshu Liu1, Peng Zhang2, Wenjun Huang1,3
1The Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Insti.
Insights
The transcription factor p53 enhances cardiomyocyte differentiation from human induced pluripotent stem cells (hiPSC). P53 promotes this process by upregulating WNT3, which is crucial for mesendodermal specification and cardiac development.
Area of Science:
- Stem cell biology
- Cardiovascular research
- Developmental biology
Background:
- Small molecule modulation of signaling pathways is effective for inducing cardiomyocytes from human induced pluripotent stem cells (hiPSC).
- The role of transcription factors, specifically p53, in hiPSC-directed cardiomyocyte differentiation is not well understood.
- p53 is essential for early embryonic development and mesendodermal differentiation in embryonic stem cells (ESC).
Purpose of the Study:
- To investigate the hypothesis that the transcription factor p53 promotes cardiomyocyte differentiation from hiPSC.
- To elucidate the molecular mechanisms by which p53 influences hiPSC-derived cardiomyocyte generation.
Main Methods:
- Utilized the GiWi protocol for cardiomyocyte generation from hiPSC, involving temporal modulation of the Wnt signaling pathway.
- Manipulated p53 levels in hiPSC through forced expression and knockdown of endogenous p53.
- Assessed cardiomyocyte differentiation efficiency, WNT3 expression, and mesendodermal specification.
Main Results:
- Forced expression of p53 significantly improved cardiomyocyte differentiation efficiency from hiPSC.
- Knockdown of endogenous p53 decreased the yield of hiPSC-derived cardiomyocytes.
- p53 upregulated WNT3 expression, mediating increased cardiomyocyte differentiation and mesendodermal specification via Wnt signaling activation.
Conclusions:
- p53 plays a crucial role in promoting cardiomyocyte differentiation from hiPSC.
- The findings offer novel insights into the function of p53 in cardiomyocyte development and differentiation during embryogenesis.
Background And Objectives:
Manipulating different signaling pathways via small molecules could efficiently induce cardiomyocytes from human induced pluripotent stem cells (hiPSC). However, the effect of transcription factors on the hiPSC-directed cardiomyocytes differentiation remains unclear. Transcription factor, p53 has been demonstrated indispensable for the early embryonic development and mesendodermal differentiation of embryonic stem cells (ESC). We tested the hypothesis that p53 promotes cardiomyocytes differentiation from human hiPSC.
Methods And Results:
Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, we demonstrated that forced expression of p53 in hiPSC remarkably improved the differentiation efficiency of cardiomyocytes from hiPSC, whereas knockdown endogenous p53 decreased the yield of cardiomyocytes. This p53-mediated increased cardiomyocyte differentiation was mediated through WNT3, as evidenced by that overexpression of p53 upregulated the expression of WNT3, and knockdown of p53 decreased the WNT3 expression. Mechanistic analysis showed that the increased cardiomyocyte differentiation partially depended on the amplified mesendodermal specification resulted from p53-mediated activation of WNT3-mediated Wnt signaling. Consistently, endogenous WNT3 knockdown significantly ameliorated mesendodermal specification and subsequent cardiomyocyte differentiation.
Conclusions:
These results provide a novel insight into the potential effect of p53 on the development and differentiation of cardiomyocyte during embryogenesis.
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