Haematopoietic ESL-1 enables stem cell proliferation in the bone marrow by limiting TGFß availability.
Nat Commun
; 7: 10222, 2016 Jan 08.
Article
en En
| MEDLINE
| ID: mdl-26742601
ABSTRACT
The life-long maintenance of haematopoietic stem and progenitor cells (HSPCs) critically relies on environmental signals produced by cells that constitute the haematopoietic niche. Here we report a cell-intrinsic mechanism whereby haematopoietic cells limit proliferation within the bone marrow, and show that this pathway is repressed by E-selectin ligand 1 (ESL-1). Mice deficient in ESL-1 display aberrant HSPC quiescence, expansion of the immature pool and reduction in niche size. Remarkably, the traits were transplantable and dominant when mutant and wild-type precursors coexisted in the same environment, but were independent of E-selectin, the vascular receptor for ESL-1. Instead, quiescence is generated by unrestrained production of the cytokine TGFß by mutant HSPC, and in vivo or in vitro blockade of the cytokine completely restores the homeostatic properties of the haematopoietic niche. These findings reveal that haematopoietic cells, including the more primitive compartment, can actively shape their own environment.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sialoglicoproteínas
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Médula Ósea
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Células Madre Hematopoyéticas
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Receptores de Factores de Crecimiento de Fibroblastos
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Quimiocinas
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Proliferación Celular
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Factor de Crecimiento Transformador beta1
Límite:
Animals
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
España