RT Journal Article
T1 RUNX1c Regulates Hematopoietic Differentiation of Human Pluripotent Stem Cells Possibly in Cooperation with Proinflammatory Signaling.
A1 Navarro-Montero, Oscar
A1 Ayllon, Veronica
A1 Lamolda, Mar
A1 López-Onieva, Lourdes
A1 Montes, Rosa
A1 Bueno, Clara
A1 Ng, Elizabeth
A1 Guerrero-Carreno, Xiomara
A1 Romero, Tamara
A1 Romero-Moya, Damià
A1 Stanley, Ed
A1 Elefanty, Andrew
A1 Ramos-Mejia, Verónica
A1 Menendez, Pablo
A1 Real, Pedro J
K1 Hematoendothelial precursors
K1 Hematopoiesis
K1 Human ESC
K1 Human PSC
K1 RUNX1c
AB 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;35:2253-2266.
YR 2017
FD 2017-09-23
LK http://hdl.handle.net/10668/11555
UL http://hdl.handle.net/10668/11555
LA en
DS RISalud
RD Mar 14, 2025