부산대학교 도서관

Runt‐related transcription factor 1 (Runx1) is a master hematopoietic transcription factor essential for hematopoietic stem cell (HSC) emergence. Runx1‐deficient mice die during early embryogenesis due to the inability to establish definitive hematopoiesis. Here, we have used human pluripotent stem cells (hPSCs) as model to study the role of RUNX1 in human embryonic hematopoiesis. Although the three RUNX1isoforms a, b, and cwere induced in CD45+ hematopoietic cells, RUNX1cwas the only isoform induced in hematoendothelial progenitors (HEPs)/hemogenic endothelium. Constitutive expression of RUNX1cin human embryonic stem cells enhanced the appearance of HEPs, including hemogenic (CD43+) HEPs and promoted subsequent differentiation into blood cells. Conversely, specific deletion of RUNX1cdramatically reduced the generation of hematopoietic cells from HEPs, indicating that RUNX1cis a master regulator of human hematopoietic development. Gene expression profiling of HEPs revealed a RUNX1c‐induced proinflammatory molecular signature, supporting previous studies demonstrating proinflammatory signaling as a regulator of HSC emergence. Collectively, RUNX1corchestrates hematopoietic specification of hPSCs, possibly in cooperation with proinflammatory signaling. StemCells2017;35:2253–2266 The transcription factor RUNX1cregulates human early blood specification. RUNX1c, possibly in cooperation with proinflammatory signals, enhances the emergence blood derivatives from hPSC cultures.