Sox2 Acts through Sox21 to Regulate Transcription in Pluripotent and Differentiated Cells

SummarySox2 is an important transcriptional regulator in embryonic and adult stem cells [1–4]. Recently, Sox2 was identified as an oncogene in many endodermal cancers, including colon cancer [5–8]. There is great interest in how Sox2 cooperates with other transcription factors to regulate stem cell renewal, differentiation, and reprogramming [9]. However, we still lack a general understanding of Sox2 transcriptional action. To determine transcriptional partners of Sox2 in adult cells, we generated mice where gene expression could be induced by an externally applied stimulus. We analyzed the consequences in the intestine where cell turnover is rapid. Sox2 expression, but not Oct4, specifically increased the numbers of stem cells and repressed Cdx2, a master regulator of endodermal identity. In vivo studies demonstrated that Sox21, another member of the SoxB gene family, was a specific, immediate, and cell-autonomous target of Sox2 in intestinal stem cells. In vitro experiments showed that Sox21 was sufficient to repress Cdx2 in colon cancer cells and in pluripotent stem cells. Sox21 was also specifically induced by Sox2 in fibroblasts and inhibition of Sox21 blocked reprogramming to the pluripotent state. These results show that transcriptional induction of Sox21 is a rapid and general mediator of the effects of Sox2 on cell identity in a wide range of cell types

Vitronectin promotes oligodendrocyte differentiation during neurogenesis of human embryonic stem cells

We demonstrate enhanced differentiation of oligodendrocytes during neurogenesis of human embryonic stem cells (hESCs) using an extracellular matrix protein, vitronectin (VN). We show that VN is expressed in the ventral part of the developing human spinal cord. Combined treatment of retinoic acid, sonic hedgehog, and noggin in the presence of VN allows hESCs to differentiate into O4-positive oligodendrocytes. Particularly, VN profoundly promotes the derivation of oligodendrocyte progenitors that proliferate and differentiate into oligodendrocytes in response to mitogenic and survival factors. These results support the beneficial effect of VN on oligodendrocytic differentiation of hESCs.This research was supported by the Seoul Research and Business Development Program (10574) and by a Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea Government(MOST) (R01-2006-000-11364-0)

Vitronectin promotes oligodendrocyte differentiation during neurogenesis of human embryonic stem cells

We demonstrate enhanced differentiation of oligodendrocytes during neurogenesis of human embryonic stem cells (hESCs) using an extracellular matrix protein, vitronectin (VN). We show that VN is expressed in the ventral part of the developing human spinal cord. Combined treatment of retinoic acid, sonic hedgehog, and noggin in the presence of VN allows hESCs to differentiate into O4-positive oligodendrocytes. Particularly, VN profoundly promotes the derivation of oligodendrocyte progenitors that proliferate and differentiate into oligodendrocytes in response to mitogenic and survival factors. These results support the beneficial effect of VN on oligodendrocytic differentiation of hESCs