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Cathepsin A regulates pluripotency, proliferation and differentiation in mouse embryonic stem cells
Author(s) -
Park Song,
Huang Hai,
Kwon Wookbong,
Kim HeeYeon,
Park JinKyu,
Han Jee Eun,
Cho GilJae,
Han SeHyeon,
Sung Yonghun,
Ryoo Zae Young,
Kim Myoung Ok,
Choi SeongKyoon
Publication year - 2021
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3554
Subject(s) - embryonic stem cell , microbiology and biotechnology , cathepsin , stem cell , cathepsin d , gene knockdown , cellular differentiation , homeobox protein nanog , induced pluripotent stem cell , rex1 , biology , chemistry , cancer research , cell culture , biochemistry , genetics , enzyme , gene
Mouse embryonic stem cells (mESCs) are pluripotent cells that possess the ability to self‐renew and differentiate into three germ layers. Owing to these characteristics, mESCs act as important models for stem cell research and are being used in many clinical applications. Among the many cathepsins, cathepsin A (Ctsa), a serine protease, affects the function and properties of stem cells. However, studies on the role of Ctsa in stem cells are limited. Here, we observed a significant increase in Ctsa expression during mESC differentiation at protein levels. Furthermore, we established Ctsa knockdown mESCs. Ctsa knockdown led to Erk1/2 phosphorylation, which in turn inhibited the pluripotency of mESCs and induced G2/M cell cycle arrest to inhibit mESC proliferation. The knockdown also induced abnormal differentiation in mESCs and aberrant expression of differentiation markers. Furthermore, we identified inhibition of teratoma formation in nude mice. Our results suggested that Ctsa affects mESC pluripotency, proliferation, cell cycle and differentiation, and highlighted the potential of Ctsa to act as a core factor that can regulate various mESC properties. Significance of the study Our results indicate that cathepsin A (Ctsa) affects the properties of mESCs. Inhibition of Ctsa resulted in a decrease in the pluripotency of mouse embryonic stem cells (mESCs). Further, Ctsa suppression resulted in decreased proliferation via cell cycle arrest. Moreover, Ctsa inhibition reduced differentiation abilities and formation of teratoma in mESCs. Our results demonstrated that Ctsa is an important factor controlling mESC abilities.