アクティブボード・２０１５年　６月
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研究発表を行った学会；
・Keystone Symposia on "Hematopoiesis", 2015
　２０１５年　２月２２日〜２７日（横浜）
タイトル；Cxcr4 signaling regulates the bipotential status of hemogenic endothelial cells.
発表者；Tanzir Ahmed　氏
　　　（熊本大学　発生医学研究所　組織幹細胞分野）
Abstract；
The origin of hematopoietic stem cells (HSCs) is considered to be hemogenic endothelial cells (HECs) located in the aorta-gonad-mesonephros region. HECs are phenotypically endothelial cells (ECs) with both hematopoietic and endothelial potential (bipotent) and some of them being the precursor of HSCs. Although bipotential progenitor cells have been reported from VE-cadherin+ cells in differentiating embryonic stem cells (ESCs), the molecular basis of the regulation of bipotentiality has not been clearly characterized yet. We sought for an enriched HEC population from CD45-CD31+VE-cad+ ECs from ESC culture. Then separated by CD41 expression, the VE-cad+CD41+ subpopulation is found highly enriched for both hematopoietic and EC progenitors. VE-cad+CD41+ cells express transcription factors of EC signature; Sox17, Etv2, Foxc2 and COUP-TF2 and also those involved in hematopoietic specification; Runx1 and Tal1. Bipotentiality of VE-cad+CD41+ cells is confirmed at the single cell level with an estimated frequency of 1 bipotent progenitor out of 38 cells indicating that this fraction represents the true HECs.
To induce HSCs from ESCs, it is essential to control the bipotent status of HECs. To modulate the differentiation of CD41+ HECs and to enrich the frequency of bipotent progenitors, we checked surface expression of several receptors. Expression of chemokine receptor Cxcr4 on HECs was critical as bipotent progenitor frequency further enriched to 1 in 20 in CD41+Cxcr4+ subfraction. We added Cxcr4 ligand, Cxcl12 during the generation of CD41+Cxcr4+ cells in the ESC culture to check the functional role on bipotent status of HECs. Cxcl12 stimulation reduced the frequency of bipotent progenitors suggesting a facilitated differentiation toward either lineage. This in vitro model of Cxcl12-Cxcr4 regulation of bipotential HECs should provide us the means to control the HEC status and the induction of transplantable HSCs from ESCs.