Abstract| Volume 43, ISSUE 9, SUPPLEMENT , S85, September 2015

SOX17 is critical for the maintenance of stem cell phenotype of intra-aortic hematopoietic clusters of cells in the aorta-gonad-mesonephros region

      Definitive hematopoiesis is firstly detected in the aorta-gonad-mesonephros (AGM) region at around E10.5, where intra-aortic cell clusters are observed. These clusters are known to contain hematopoietic stem and progenitor cells (HSPCs), but how they maintain the HSPC phenotype and how they undergo differentiation remained unclear. Here we show that Sox17, a transcription factor, was expressed in cell clusters of HSPCs in the dorsal aorta. Overexpression of the Sox17 protein in the FACS-sorted CD45lowc-Kithigh cells from the AGM region, which are a cellular component of intra-aortic cell clusters, inhibited differentiation of HSPCs and led to repetitive formation of cell clusters during several passages of the cocultures with stromal cells. Cluster-forming cells with constitutive Sox17 expression retained a long-term bone marrow reconstitution activity in vivo. During the coculture, shutdown of the expression of transduced Sox17 gene induced the hematopoietic differentiation. These results indicate that Sox17 is critical for the maintenance of cell clusters containing HSPCs in the AGM region. Moreover, we and other groups showed that vascular endothelial-cadherin (VEC) was highly expressed in Sox17-transduced cells. Effective shRNA for VEC suppressed the formation of Sox17-transduced cell clusters and induced the hematopoietic differentiation. Taken together, our data suggest that the Sox17 has an ability to maintain an undifferentiated state in the intra-aortic cell clusters.