Protein quality control of cell stemness
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REVIEW
Open Access
Protein quality control of cell stemness Pengze Yan1,2, Jie Ren2,3,4,5, Weiqi Zhang2,3,4,5*, Jing Qu2,5,6* and Guang-Hui Liu1,2,5,7*
Abstract Protein quality control (PQC) systems play essential roles in the recognition, refolding and clearance of aberrant proteins, thus ensuring cellular protein homeostasis, or proteostasis. Especially, continued proliferation and differentiation of stem cells require a high rate of translation; therefore, accurate PQC systems are essential to maintain stem cell function. Growing evidence suggested crucial roles of PQC systems in regulating the stemness and differentiation of stem cells. This review focuses on current knowledge regarding the components of the proteostasis network in stem cells, and the importance of proteostasis in maintaining stem cell identity and regenerative functions. A complete understanding of this process might uncover potential applications in aging intervention and aging-related diseases. Keywords: Protein quality control, Stem cells, Stemness, Chaperones, Unfolded protein response, Ubiquitinproteasome system, Autophagy
Background Stem cells serve as the origin of a multicellular organism. They can divide to give rise to daughter cells that remain as stem cells or become differentiated with a specific function. The multi-differentiation potential gives stem cells unparalleled advantages in regenerative medicine. Originally, stem cells can be categorized into two main groups: embryonic stem cells (ESCs) and adult stem cells (ASCs). Yet with the development of reprogramming technologies, somatic cells can also be reprogrammed into ESC-like cells, termed as induced pluripotent stem cells (iPSCs). Collectively, ESCs and iPSCs are referred to as pluripotent stem cells (PSCs) because of their high capacity for selfrenewal and their ability for multipotent differentiation, offering far-reaching potential in disease modeling and transplant therapies (Evans and Kaufman, 1981; Shu et al., 2013; Yamanaka, 2009). On the other hand, ASCs are undifferentiated cells distributed throughout the body, and have the ability to differentiate into several restricted cell types and to participate in tissue regeneration (Passier and * Correspondence: [email protected]; [email protected]; [email protected] 2 University of Chinese Academy of Sciences, Beijing 100049, China 1 State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China Full list of author information is available at the end of the article
Mummery, 2003; Wagers and Weissman, 2004). Due to their lower immunogenicity and higher safety profile, certain ASCs (eg. MSCs) are recognized as the most promising source for cell therapy (Kode et al., 2009; Pessina and Gribaldo, 2006). Researches focused on stem cells have attracted much attention in recent years, with a particular focus on the transcription factor networks that regulate their stemness and differentiation (Avilion et al., 2003; Chambers et al., 2003; Cui et al., 2018; Nichols et al., 199
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