1. RUNX1c Regulates Hematopoietic Differentiation of Human Pluripotent Stem Cells Possibly in Cooperation with Proinflammatory Signaling
- Author
-
Elizabeth Ng, Ed Stanley, Pablo Menendez, Verónica Ramos-Mejía, Clara Bueno, Damia Romero-Moya, Oscar Navarro-Montero, Tamara Romero, Pedro J. Real, Xiomara Guerrero-Carreno, Lourdes Lopez-Onieva, Verónica Ayllón, Rosa Montes, Mar Lamolda, and Andrew G. Elefanty
- Subjects
Pluripotent Stem Cells ,0301 basic medicine ,Biology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,medicine ,Animals ,Humans ,Progenitor cell ,Induced pluripotent stem cell ,Human ESC ,Hemogenic endothelium ,Human PSC ,Gene Expression Profiling ,Hematopoietic stem cell ,Cell Differentiation ,Cell Biology ,Embryonic stem cell ,Hematopoiesis ,Cell biology ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,RUNX1 ,chemistry ,Core Binding Factor Alpha 2 Subunit ,Immunology ,Molecular Medicine ,Hematoendothelial precursors ,Stem cell ,Signal Transduction ,RUNX1c ,Developmental Biology - Abstract
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.
- Published
- 2017
- Full Text
- View/download PDF