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

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 proliferationindependent 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.

Mettl14-driven senescence-associated secretory phenotype facilitates somatic cell reprogramming

“…To investigate the effect of m 6 A level on the reprogramming process, we screened the m 6 A writers and erasers using reprogrammable mouse embryonic fibroblasts (MEFs) from Rosa26-M2rtTA; Col1a1-4F2A; Oct4-GFP + transgenic mice (Carey et al, 2010). Exogenous doxycycline (Dox) can induce the expression of OSKM and reprogram MEFs into Oct4-GFP + iPSCs, as previously reported (Wu et al, 2017(Wu et al, , 2021. We found that Mettl3 and Mettl14 expression significantly increased the number of Oct4 1D).…”

Corrigendum

“…There are some mistakes in the figure legends of Figure 1C and Figures S1B-E of Wu et al 1 The correct figure legends are below: The authors apologize for the errors.…”

The occurrence and development of induced pluripotent stem cells

“…The study by Feng et al, 2022 showed that in the early stages of reprogramming and iPSC generation, knocking down Sin3a significantly disrupts MET, and disrupting the interaction between Sin3a and Tet1 can significantly block the generation of MET and iPSCs. Wu et al, 2021 demonstrated that when coexpressed with OSKM, Surf4 can activate the response to ER stress in the early stages of reprogramming, significantly promoting the generation of iPSCs without relying on proliferation. Wang et al, 2021 showed that short-term induction of the local expression of OSKM in muscle fibers can promote the activation of muscle stem cells or satellite cells (SCs), thereby accelerating muscle regeneration in young mice, which may promote tissue regeneration by altering the stem cell niche.…”