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LncRNA ZFAS1 regulates cardiomyocyte differentiation of human embryonic stem cells

YANG CAO1,#, YINING LIU1,#, YANG YU1, XIAOFEI GUO1, XIUXIU WANG1, WENYA MA1, HANJING LI2, ZHONGYU REN2, XINLU GAO2, SIJIA LI2, HAOYU JI2, HONGYANG CHEN2, HONG YAN2, YANAN TIAN2, XIN WANG2, BENZHI CAI1,2,*

1 Department of Pharmacy, The Second Affiliated Hospital of Harbin Medical University (Institute of Clinical Pharmacy, The University Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions), Harbin, 150086, China
2 Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, 150081, China

* Corresponding Author: BENZHI CAI. Email: email
# The first two authors contributed equally to this work

BIOCELL 2023, 47(6), 1407-1416. https://doi.org/10.32604/biocell.2023.029080

Abstract

Background: Cardiomyocytes derived from human embryonic stem cells (hESCs) are regulated by complex and stringent gene networks during differentiation. Long non-coding RNAs (lncRNAs) exert critical epigenetic regulatory functions in multiple differentiation processes. However, the involvement of lncRNAs in the differentiation of hESCs into cardiomyocytes has not yet been fully elucidated. Here, we identified the key roles of ZFAS1 (lncRNA zinc finger antisense 1) in the differentiation of cardiomyocytes from hESCs. Methods: A model of cardiomyocyte differentiation from stem cells was established using the monolayer differentiation method, and the number of beating hESCs-derived cardiomyocytes was calculated. Gene expression was analyzed by quantitative real-time PCR (qRT-PCR). Immunofluorescence assays were performed to assess the expression of cardiac troponin T (cTnT) and α-actinin protein in cardiomyocytes. Results: qRT-PCR showed that ZFAS1 expression in the mesoderm was significantly higher than that in embryonic stem cells, cardiac progenitor cells, and cardiomyocytes. Knockdown of ZFAS1 inhibited cardiomyocyte differentiation from hESCs, which was characterized by reduced expression of the cardiac-specific markers cTnT, α-actinin, myosin heavy chain 6 (MYH6), and myosin heavy chain 7 (MYH7). In contrast, ZFAS1 overexpression remarkably increased the percentage of spontaneously beating cardiomyocytes. In terms of the mechanism, we found that ZFAS1 is an antisense lncRNA at the 5′ end of the protein-coding gene ZNFX1. Knockdown of ZFAS1 could increase the mRNA expression level of ZNFX1. Furthermore, qRT-PCR demonstrated that the silencing of ZNFX1 led to an increase in cardiac-specific markers that predicted the promotion of cardiomyocyte differentiation. Conclusion: Altogether, these data suggest that lncRNA-ZFAS1 is required for cardiac differentiation by functionally inhibiting the expression of ZNFX1, which may provide a reference for the treatment of heart disease to a certain extent.

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APA Style
CAO, Y., LIU, Y., YU, Y., GUO, X., WANG, X. et al. (2023). Lncrna <i>zfas1</i> regulates cardiomyocyte differentiation of human embryonic stem cells. BIOCELL, 47(6), 1407-1416. https://doi.org/10.32604/biocell.2023.029080
Vancouver Style
CAO Y, LIU Y, YU Y, GUO X, WANG X, MA W, et al. Lncrna <i>zfas1</i> regulates cardiomyocyte differentiation of human embryonic stem cells. BIOCELL . 2023;47(6):1407-1416 https://doi.org/10.32604/biocell.2023.029080
IEEE Style
Y. CAO et al., "LncRNA <i>ZFAS1</i> regulates cardiomyocyte differentiation of human embryonic stem cells," BIOCELL , vol. 47, no. 6, pp. 1407-1416. 2023. https://doi.org/10.32604/biocell.2023.029080



cc This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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