Hlf marks the developmental pathway for hematopoietic stem cells but not for erythro-myeloid progenitors.
J Exp Med
; 216(7): 1599-1614, 2019 07 01.
Article
en En
| MEDLINE
| ID: mdl-31076455
ABSTRACT
Before the emergence of hematopoietic stem cells (HSCs), lineage-restricted progenitors, such as erythro-myeloid progenitors (EMPs), are detected in the embryo or in pluripotent stem cell cultures in vitro. Although both HSCs and EMPs are derived from hemogenic endothelium, it remains unclear how and when these two developmental programs are segregated during ontogeny. Here, we show that hepatic leukemia factor (Hlf) expression specifically marks a developmental continuum between HSC precursors and HSCs. Using the Hlf-tdTomato reporter mouse, we found that Hlf is expressed in intra-aortic hematopoietic clusters and fetal liver HSCs. In contrast, EMPs and yolk sac hematopoietic clusters before embryonic day 9.5 do not express Hlf HSC specification, regulated by the Evi-1/Hlf axis, is activated only within Hlf+ nascent hematopoietic clusters. These results strongly suggest that HSCs and EMPs are generated from distinct cohorts of hemogenic endothelium. Selective induction of the Hlf+ lineage pathway may lead to the in vitro generation of HSCs from pluripotent stem cells.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Células Madre Hematopoyéticas
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Células Precursoras Eritroides
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Células Progenitoras Mieloides
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico
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Hematopoyesis
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón