2. Academic Validation
  3. Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress

Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress

  • Cell Prolif. 2021 Nov;54(11):e13133. doi: 10.1111/cpr.13133.
Li Wu 1,  Shengxiang He 1 2,  Wen Ye 1,  Jiacheng Shen 1,  Kun Zhao 1,  Yanping Zhang 1,  Ran Zhang 2,  Junhao Wei 1,  Shuyuan Cao 1,  Kang Chen 1,  Rongrong Le 1 3,  Chenxiang Xi 1,  Xiaochen Kou 1 3,  Yanhong Zhao 1 3,  Hong Wang 1 3,  Lan Kang 3 4,  Shaorong Gao 1 3
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • 2 Anhui Toneker Biotechnology Co., Ltd., Jinzhai, China.
  • 3 Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China.
  • 4 Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Institute for Regenerative Medicine, Shanghai East Hospital, Tongji University, Shanghai, China.
PMID: 34585448 DOI: 10.1111/cpr.13133
Abstract

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.

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