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Surf4 facilitates reprogramming by activating the cellular response to endoplasmic reticulum stress
Li Wu1, Shengxiang He1,2, Wen Ye1
1Shanghai 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.
Cell Proliferation
|September 29, 2021
Summary
Surfeit locus protein 4 (Surf4) enhances induced pluripotent stem cell (iPSC) generation by activating endoplasmic reticulum (ER) stress responses. This maternal factor promotes reprogramming through the unfolded protein response pathway.
Area of Science:
- Cellular reprogramming
- Stem cell biology
- Molecular mechanisms of development
Background:
- Maternal factors in oocytes are crucial for early development and reprogramming.
- Surfeit locus protein 4 (Surf4) is a maternal factor known to facilitate induced pluripotent stem cell (iPSC) generation.
- The precise mechanism by which Surf4 enhances reprogramming remains unclear.
Purpose of the Study:
- To elucidate the functional mechanism of Surf4 in somatic cell reprogramming.
- To investigate how Surf4 influences the efficiency and characteristics of iPSC generation.
- To identify downstream pathways modulated by Surf4 during reprogramming.
Main Methods:
- Utilized a secondary reprogramming system with mouse embryonic fibroblasts.
- Assessed iPSC generation efficiency via Alkaline Phosphatase staining, qPCR, and immunofluorescence.
- Evaluated iPSC differentiation potential using embryoid body and teratoma formation assays.
- Analyzed downstream targets of Surf4 using RNA-seq, qPCR, and Western blot.
Main Results:
- Surf4 significantly enhanced iPSC generation independently of cell proliferation.
- Co-expression of Surf4 with reprogramming factors (OSKM) activated endoplasmic reticulum (ER) stress responses early in reprogramming.
- Key ER stress mediators, Hspa5 and spliced Xbp1 (sXbp1), mimicked Surf4's reprogramming-enhancing effects.
- Inhibition of the unfolded protein response abrogated Surf4's beneficial impact on reprogramming.
Conclusions:
- Surf4 promotes somatic cell reprogramming by activating the endoplasmic reticulum (ER) stress response.
- The unfolded protein response pathway is critical for Surf4-mediated enhancement of iPSC generation.
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