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Temporal Control of the WNT Signaling Pathway During Cardiac Differentiation Impacts Upon the Maturation State of Human Pluripotent Stem Cell Derived Cardiomyocytes.
Tsoi, Chantelle; Deng, Ruixia; Kwok, Maxwell; Yan, Bin; Lee, Carrie; Li, Hung Sing; Ma, Chloe Ho Yi; Luo, Ruibang; Leung, Kam Tong; Chan, Godfrey Chi-Fung; Chow, Larry Ming-Cheung; Poon, Ellen N.
Afiliación
  • Tsoi C; Centre for Cardiovascular Genomics and Medicine, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong (CUHK), Shatin, Hong Kong SAR, China.
  • Deng R; Hong Kong Hub of Paediatric Excellence (HK HOPE), CUHK, Shatin, Hong Kong SAR, China.
  • Kwok M; Centre for Cardiovascular Genomics and Medicine, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong (CUHK), Shatin, Hong Kong SAR, China.
  • Yan B; Hong Kong Hub of Paediatric Excellence (HK HOPE), CUHK, Shatin, Hong Kong SAR, China.
  • Lee C; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.
  • Li HS; Hong Kong Hub of Paediatric Excellence (HK HOPE), CUHK, Shatin, Hong Kong SAR, China.
  • Ma CHY; Department of Medicine and Therapeutics, CUHK, Shatin, Hong Kong SAR, China.
  • Luo R; Department of Computer Science, Faculty of Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
  • Leung KT; Centre for Cardiovascular Genomics and Medicine, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong (CUHK), Shatin, Hong Kong SAR, China.
  • Chan GC; Hong Kong Hub of Paediatric Excellence (HK HOPE), CUHK, Shatin, Hong Kong SAR, China.
  • Chow LM; Centre for Cardiovascular Genomics and Medicine, Lui Che Woo Institute of Innovative Medicine, The Chinese University of Hong Kong (CUHK), Shatin, Hong Kong SAR, China.
  • Poon EN; Hong Kong Hub of Paediatric Excellence (HK HOPE), CUHK, Shatin, Hong Kong SAR, China.
Front Mol Biosci ; 9: 714008, 2022.
Article en En | MEDLINE | ID: mdl-35402504
Inefficient differentiation and insufficient maturation are barriers to the application of human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) for research and therapy. Great strides have been made to the former, and multiple groups have reported cardiac differentiation protocol that can generate hPSC-CMs at high efficiency. Although many such protocols are based on the modulation of the WNT signaling pathway, they differ in their timing and in the WNT inhibitors used. Little is currently known about whether and how conditions of differentiation affect cardiac maturation. Here we adapted multiple cardiac differentiation protocols to improve cost-effectiveness and consistency, and compared the properties of the hPSC-CMs generated. Our results showed that the schedule of differentiation, but not the choice of WNT inhibitors, was a critical determinant not only of differentiation efficiency, which was expected, but also CM maturation. Among cultures with comparable purity, hPSC-CMs generated with different differentiation schedules vary in the expression of genes which are important for developmental maturation, and in their structural, metabolic, calcium transient and proliferative properties. In summary, we demonstrated that simple changes in the schedule of cardiac differentiation could promote maturation. To this end, we have optimized a cardiac differentiation protocol that can simultaneously achieve high differentiation efficiency and enhanced developmental maturation. Our findings would advance the production of hPSC-CMs for research and therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline Idioma: En Revista: Front Mol Biosci Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Guideline Idioma: En Revista: Front Mol Biosci Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza