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SNTA1-deficient human cardiomyocytes demonstrate hypertrophic phenotype and calcium handling disorder.
Dong, Tao; Zhao, Yan; Jin, Hai-Feng; Shen, Lei; Lin, Yan; Si, Long-Long; Chen, Li; Liu, Ji-Cheng.
Afiliación
  • Dong T; Basic Medicine School, Qiqihar Medical University, 333 Bukui Street, Qiqihar, 161006, Heilongjiang, China. 924516982@qq.com.
  • Zhao Y; College of Life Science and Agroforestry, Qiqihar University, Qiqihar, 161006, Heilongjiang, China.
  • Jin HF; Basic Medicine School, Qiqihar Medical University, 333 Bukui Street, Qiqihar, 161006, Heilongjiang, China.
  • Shen L; Basic Medicine School, Qiqihar Medical University, 333 Bukui Street, Qiqihar, 161006, Heilongjiang, China.
  • Lin Y; Basic Medicine School, Qiqihar Medical University, 333 Bukui Street, Qiqihar, 161006, Heilongjiang, China.
  • Si LL; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • Chen L; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • Liu JC; Qiqihar Institute of Medical and Pharmaceutical Sciences, Qiqihar Medical University, 333 Bukui Street, Qiqihar, 161006, Heilongjiang, China. jcliu@qmu.edu.cn.
Stem Cell Res Ther ; 13(1): 288, 2022 06 30.
Article en En | MEDLINE | ID: mdl-35773684
BACKGROUND: α-1-syntrophin (SNTA1), a protein encoded by SNTA1, is highly expressed in human cardiomyocytes. Mutations in SNTA1 are associated with arrhythmia and cardiomyopathy. Previous research on SNTA1 has been based on non-human cardiomyocytes. This study was designed to identify the phenotype of SNTA1-deficiency using human cardiomyocytes. METHODS: SNTA1 was knocked out in the H9 embryonic stem cell line using the CRISPR-Cas9 system. H9SNTA1KO cells were then induced to differentiate into cardiomyocytes using small molecule inhibitors. The phenotypic discrepancies associated with SNTA1-deficient cardiomyocytes were investigated. RESULTS: SNTA1 was truncated at the 149th amino acid position of PH1 domain by a stop codon (TGA) using the CRISPR-Cas9 system. SNTA1-deficiency did not affect the pluripotency of H9SNTA1KO, and they retain their in vitro ability to differentiate into cardiomyocytes. However, H9SNTA1KO derived cardiomyocytes exhibited hypertrophic phenotype, lower cardiac contractility, weak calcium transient intensity, and lower level of calcium in the sarcoplasmic reticulum. Early treatment of SNTA1-deficient cardiomyocytes with ranolazine improved the calcium transient intensity and cardiac contractility. CONCLUSION: SNTA1-deficient cardiomyocytes can be used to research the etiology, pathogenesis, and potential therapies for myocardial diseases. The SNTA1-deficient cardiomyocyte model suggests that the maintenance of cardiac calcium homeostasis is a key target in the treatment of myocardial-related diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcio / Miocitos Cardíacos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Stem Cell Res Ther Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Calcio / Miocitos Cardíacos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Stem Cell Res Ther Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido