Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment.
Cell
; 129(6): 1081-95, 2007 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-17574022
ABSTRACT
Hematopoiesis is maintained by stem cells (HSCs) that undergo fate decisions by integrating intrinsic and extrinsic signals, with the latter derived from the bone marrow (BM) microenvironment. Cell-cycle regulation can modulate stem cell fate, but it is unknown whether this represents an intrinsic or extrinsic effector of fate decisions. We have investigated the role of the retinoblastoma protein (RB), a central regulator of the cell cycle, in hematopoiesis. Widespread inactivation of RB in the murine hematopoietic system resulted in profound myeloproliferation. HSCs were lost from the BM due to mobilization to extramedullary sites and differentiation. This phenotype was not intrinsic to HSCs, but, rather, was the consequence of an RB-dependent interaction between myeloid-derived cells and the microenvironment. These findings demonstrate that myeloproliferation may result from perturbed interactions between hematopoietic cells and the niche. Therefore, RB extrinsically regulates HSCs by maintaining the capacity of the BM to support normal hematopoiesis and HSCs.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Médula Ósea
/
Células Madre Hematopoyéticas
/
Regulación de la Expresión Génica
/
Proteína de Retinoblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos