Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress.
Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress.
复制标题
Surf4 通过激活细胞对内质网应激的反应来促进重编程
DOI：
10.1111/cpr.13133
复制
发表时间：
2021-11
影响因子：
8.5
通讯作者：
Gao S
中科院分区：
文献类型：
--
作者：
Wu L;He S;Ye W;Shen J;Zhao K;Zhang Y;Zhang R;Wei J;Cao S;Chen K;Le R;Xi C;Kou X;Zhao Y;Wang H;Kang L;Gao S
富含于卵母细胞中的母体因子作为体细胞重编程中可能的关键因子引起了人们极大的兴趣。我们发现，过量基因座蛋白4（Surf 4），一个母亲的因素，可以促进诱导多能干细胞（iPSCs）的产生以前，但机制仍然是难以捉摸的。本研究利用二次重编程系统研究了Surf 4在体细胞重编程中的功能和机制。碱性磷酸酶（AP）染色、qPCR和相关标志物表达的免疫荧光（IF）染色用于评估源自小鼠胚胎成纤维细胞的iPSC的效率。进行胚状体和畸胎瘤形成测定以评估iPSC系的分化能力。应用RNA-seq、qPCR和蛋白质印迹分析来验证Surf 4的下游靶标。Surf 4可以显著促进iPSC以增殖非依赖性方式产生。当与Oct 4、Sox 2、Klf 4和c-Myc（OSKM）共表达时，Surf 4可以在重编程的早期阶段激活对内质网（ER）应激的反应。我们进一步证明，Hspa 5，一个主要的ER分子伴侣，和Xbp 1（sXbp 1），一个主要的ER应激介质的活性剪接形式，可以模仿体细胞重编程的Surf 4的影响。一致地，阻断未折叠的蛋白质应答损害了Surf 4对重编程的作用。Surf 4通过激活对内质网应激的反应来促进体细胞重编程。母体因子Surf 4可以显著促进诱导多能干细胞（iPSC）以增殖非依赖性方式产生。当与Oct 4、Sox 2、Klf 4和c-Myc（OSKM）共表达时，Surf 4可以在重编程的早期阶段激活对内质网（ER）应激的反应。
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. 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. 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. Surf4 promotes somatic cell reprogramming by activating the response to ER stress. Maternal factor Surf4 can significantly facilitate the generation of induced pluripotent stem cells (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.
登录
查看更多内容
影响因子：
56.9
作者：
Gonzalez-Munoz, Elena;Arboleda-Estudillo, Yohanna;Cibelli, Jose B.
通讯作者：
Cibelli, Jose B.
影响因子：
64.5
作者：
Ang YS;Tsai SY;Lee DF;Monk J;Su J;Ratnakumar K;Ding J;Ge Y;Darr H;Chang B;Wang J;Rendl M;Bernstein E;Schaniel C;Lemischka IR
通讯作者：
Lemischka IR
影响因子：
56.9
作者：
Belden, WJ;Barlowe, C
通讯作者：
Barlowe, C
大面积二维晶体的通用机械剥离
影响因子：
16.6
作者：
Huang, Yuan;Pan, Yu-Hao;Gao, Hong-Jun
通讯作者：
Gao, Hong-Jun
影响因子：
7.7
作者：
Emmer, Brian T.;Hesketh, Geoffrey G.;Ginsburg, David
通讯作者：
Ginsburg, David