Surf4 facilitates reprogramming by activating the cellular response to ER stress

By somatic cell nuclear transfer, the oocytes can reprogram terminally differentiated cells back to totipotent state. So the oocytes enriched maternal proteins attract great interests in exploring key factors in somatic cell reprogramming. Here, we presented a maternal factor, surfeit locus protein 4 (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 early stage of reprogramming. Besides, blocking unfolded protein response (UPR) compromised the effect of Surf4 on reprogramming. In conclusion, Surf4 serves as an activator for somatic cell reprogramming by activating the response to ER stress. Overall design: The reprogrammable MEFs derived from the R26rtTA Col1a14F2A Oct4EGFP mice, which harboring the doxycycline-inducible polycistronic 4F2A cassette (Oct4, Sox2, Klf4 and c-Myc), the constitutively expressed reverse tetracycline transactivator (rtTA) and expressed enhanced green fluorescent protein (EGFP) under the control of the Oct4 promoter and distal enhancer, were used in the experiments. The reprogrammable MEFs that were not induced with doxycycline were designated as “MEF”. The reprogrammable cells with or without Surf4's overexpression were induced with doxycycline (1ug/ml) for 3 days, which were designated as “control” and “Surf4”, respectively. The cells were harvested and performed RNA sequencing (RNA-seq)