Efficient Induction of Pluripotent Stem Cells from Granulosa Cells by Oct4 and Sox2

Abstract

Various types of somatic cells can be reprogrammed to induced pluripotent stem (iPS) cells. Somatic stem cells exhibit enhanced reprogramming efficiency by fewer factors, in contrast to fully differentiated cells. Nuclear LaminA is highly expressed in differentiated cells, and stem cells are characterized by the absence of LaminA. Granulosa cells (GCs) and cumulus cells in the ovarian follicles effectively and firstly generated cloned mice by somatic cell nuclear transfer, and these cells lack LaminA expression. We tested the hypothesis that GCs could be effectively used to generate iPS cells with fewer factors. We show that iPS cells are generated from GCs at high efficiency even with only two factors, Oct4 and Sox2, like the iPS cells generated using four Yamanaka factors. These iPS cells show pluripotency in vitro and in vivo, as evidenced by high expression of pluripotency-associated genes, Oct4, Nanog, and SSEA-1, differentiation into three embryonic germ layers by embryoid body formation and teratoma tests, as well as high efficient generation of chimeras. Moreover, the exogenous genes are effectively silenced in these iPS cells. These data provide additional evidence in supporting the notion that reduced expression of LaminA and stem cells can improve the reprogramming efficiency to pluripotency.