Verónica Ramos-Mejia, Andrew Elefanty, Ed Stanley, Damià Romero-Moya, Rosa Montes, Pedro J. Real, Mar Lamolda, Tamara Romero, Xiomara Guerrero-Carreno, Pablo Menendez, Elizabeth Ng, Veronica Ayllon, Oscar Navarro-Montero, Clara Bueno, Lourdes López-Onieva
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 RUNX1 isoforms a, b, and c were induced in CD45+ hematopoietic cells, RUNX1c was the only isoform induced in hematoendothelial progenitors (HEPs)/hemogenic endothelium. Constitutive expression of RUNX1c in human embryonic stem cells enhanced the appearance of HEPs, including hemogenic (CD43+) HEPs and promoted subsequent differentiation into blood cells. Conversely, specific deletion of RUNX1c dramatically reduced the generation of hematopoietic cells from HEPs, indicating that RUNX1c is 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, RUNX1c orchestrates hematopoietic specification of hPSCs, possibly in cooperation with proinflammatory signaling. Stem Cells 2017; 00:000–000
The transcription factor RUNX1c regulates human early blood specification. RUNX1c, possibly in cooperation with proinflammatory signals, enhances the emergence blood derivatives from hPSC cultures.