BMP and Hedgehog Regulate Distinct AGM Hematopoietic Stem Cells Ex Vivo.
Stem Cell Reports
; 6(3): 383-95, 2016 Mar 08.
Article
en En
| MEDLINE
| ID: mdl-26923823
ABSTRACT
Hematopoietic stem cells (HSC), the self-renewing cells of the adult blood differentiation hierarchy, are generated during embryonic stages. The first HSCs are produced in the aorta-gonad-mesonephros (AGM) region of the embryo through endothelial to a hematopoietic transition. BMP4 and Hedgehog affect their production and expansion, but it is unknown whether they act to affect the same HSCs. In this study using the BRE GFP reporter mouse strain that identifies BMP/Smad-activated cells, we find that the AGM harbors two types of adult-repopulating HSCs upon explant culture One type is BMP-activated and the other is a non-BMP-activated HSC type that is indirectly controlled by Hedgehog signaling through the VEGF pathway. Transcriptomic analyses demonstrate that the two HSC types express distinct but overlapping genetic programs. These results revealing the bifurcation in HSC types at early embryonic stages in the AGM explant model suggest that their development is dependent upon the signaling molecules in the microenvironment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
/
Proteínas Hedgehog
/
Proteína Morfogenética Ósea 4
/
Hematopoyesis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Stem Cell Reports
Año:
2016
Tipo del documento:
Article
País de afiliación:
Reino Unido