Open AccessSurf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress
Author(s) -
Wu Li,
He Shengxiang,
Ye Wen,
Shen Jiacheng,
Zhao Kun,
Zhang Yanping,
Zhang Ran,
Wei Junhao,
Cao Shuyuan,
Chen Kang,
Le Rongrong,
Xi Chenxiang,
Kou Xiaochen,
Zhao Yanhong,
Wang Hong,
Kang Lan,
Gao Shaorong
Publication year - 2021
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.13133
Subject(s) - reprogramming , induced pluripotent stem cell , klf4 , biology , microbiology and biotechnology , endoplasmic reticulum , somatic cell , unfolded protein response , sox2 , xbp1 , embryonic stem cell , embryoid body , cell , genetics , rna , rna splicing , gene
Objectives Maternal factors that are enriched in oocytes have attracted great interest as possible key factors in somatic cell reprogramming. We found that surfeit locus protein 4 (Surf4), a maternal factor, can facilitate the generation of induced pluripotent stem cells (iPSCs) previously, but the mechanism remains elusive. Materials and Methods In this study, we investigated the function and mechanism of Surf4 in somatic cell reprogramming using a secondary reprogramming system. Alkaline phosphatase (AP) staining, qPCR and immunofluorescence (IF) staining of expression of related markers were used to evaluate efficiency of iPSCs derived from mouse embryonic fibroblasts. Embryoid body and teratoma formation assays were performed to evaluate the differentiation ability of the iPSC lines. RNA‐seq, qPCR and western blot analysis were applied to validate the downstream targets of Surf4. Results Surf4 can significantly facilitate the generation of iPSCs in a proliferation‐independent manner. When co‐expressed with Oct4, Sox2, Klf4 and c‐Myc (OSKM), Surf4 can activate the response to endoplasmic reticulum (ER) stress at the early stage of reprogramming. We further demonstrated that Hspa5, a major ER chaperone, and the active spliced form of Xbp1 (sXbp1), a major mediator of ER stress, can mimic the effects of Surf4 on somatic cell reprogramming. Concordantly, blocking the unfolded protein response compromises the effect of Surf4 on reprogramming. Conclusions Surf4 promotes somatic cell reprogramming by activating the response to ER stress.