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Pten Regulates Cardiomyocyte Differentiation by Modulating Non-CG Methylation via Dnmt3.
Wang, Wuming; Lu, Gang; Liu, Hong-Bin; Xiong, Zhiqiang; Leung, Ho-Duen; Cao, Ruican; Pang, Alan Lap-Yin; Su, Xianwei; Law, Patrick Wai Nok; Zhao, Zhiju; Chen, Zi-Jiang; Chan, Wai-Yee.
Afiliación
  • Wang W; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • Lu G; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China.
  • Liu HB; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • Xiong Z; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China.
  • Leung HD; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • Cao R; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China.
  • Pang AL; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China.
  • Su X; SDIVF R&D Centre, 12W, Hong Kong Science Park, Shatin, Hong Kong, China.
  • Law PWN; SDIVF R&D Centre, 12W, Hong Kong Science Park, Shatin, Hong Kong, China.
  • Zhao Z; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • Chen ZJ; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250001, China.
  • Chan WY; R&D Division, TGD Life Company Limited, 15W, Hong Kong Science Park, Shatin, Hong Kong, China.
Adv Sci (Weinh) ; 8(17): e2100849, 2021 09.
Article en En | MEDLINE | ID: mdl-34247447
The regulation of cardiomyocyte differentiation is a fundamental aspect of cardiac development and regenerative medicine. PTEN plays important roles during embryonic development. However, its role in cardiomyocyte differentiation remains unknown. In this study, a low-cost protocol for cardiomyocyte differentiation from mouse embryonic stem cells (ESCs) is presented and it is shown that Pten deletion potently suppresses cardiomyocyte differentiation. Transcriptome analysis shows that the expression of a series of cardiomyocyte marker genes is downregulated in Pten-/- cardiomyocytes. Pten ablation induces Dnmt3b expression via the AKT/FoxO3a pathway and regulates the expression of a series of imprinted genes, including Igf2. Double knockout of Dnmt3l and Dnmt3b rescues the deficiency of cardiomyocyte differentiation of Pten-/- ESCs. The DNA methylomes from wild-type and Pten-/- embryoid bodies and cardiomyocytes are analyzed by whole-genome bisulfite sequencing. Pten deletion significantly promotes the non-CG (CHG and CHH) methylation levels of genomic DNA during cardiomyocyte differentiation, and the non-CG methylation levels of cardiomyocyte genes and Igf2 are increased in Pten-/- cardiomyocytes. Igf2 or Igf1r deletion also suppresses cardiomyocyte differentiation through the MAPK/ERK signaling pathway, and IGF2 supplementation partially rescues the cardiomyocyte differentiation. Finally, Pten conditional knockout mice are generated and the role of PTEN in cardiomyocyte differentiation is verified in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilasas de Modificación del ADN / Diferenciación Celular / Metilación de ADN / Miocitos Cardíacos / Fosfohidrolasa PTEN Límite: Animals Idioma: En Revista: Adv Sci (Weinh) Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Metilasas de Modificación del ADN / Diferenciación Celular / Metilación de ADN / Miocitos Cardíacos / Fosfohidrolasa PTEN Límite: Animals Idioma: En Revista: Adv Sci (Weinh) Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania