search for




 

p53 Promotes Differentiation of Cardiomyocytes from hiPSC through Wnt Signaling-Mediated Mesendodermal Differentiation
International Journal of Stem Cells
Published online June 30, 2021;  
© 2021 Korean Society for Stem Cell Research.

Yuanshu Liu1,*, Peng Zhang3,*, Wenjun Huang1,2, Feng Liu1, Dandan Long1, Wanling Peng1, Xitong Dang1, Xiaorong Zeng1, Rui Zhou1,2

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, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China
2Shaanxi Institute for Pediatric Diseases, Xi’an Key Laboratory of Children’s Health and Diseases, Department of Cardiology, Xi’an Children’s Hospital, Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, China
3Department of Anesthesiology, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
Correspondence to: Rui Zhou
Shaanxi Institute for Pediatric Diseases, Affiliated Children’s Hospital of Xi’an Jiaotong University, No. 69, Xijuyuan Lane, Lianhu District, Xi’an 710003, China
Tel: +86-029-87692102, Fax: +86-029-87692102, E-mail: zhouhuaxizhu@126.com
Co-Correspondence to Xiaorong Zeng
Institute of Cardiovascular Research, Southwest Medical University, 3-319 Zhongshan Road, Luzhou 646000, China
Tel: +86-0830-3160619, Fax: +86-0830-3160619, E-mail: zxr8818@vip.sina.com
*These authors contributed equally to this work.
Received March 13, 2021; Revised May 11, 2021; Accepted May 17, 2021.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
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.
Keywords : hiPSC, Cardiomyocytes, p53, Wnt signaling