Literature DB >> 22862945

Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways.

Marit Westerterp1, Samuel Gourion-Arsiquaud, Andrew J Murphy, Alan Shih, Serge Cremers, Ross L Levine, Alan R Tall, Laurent Yvan-Charvet.   

Abstract

Intact cholesterol homeostasis helps to maintain hematopoietic stem and multipotential progenitor cell (HSPC) quiescence. Mice with defects in cholesterol efflux pathways due to deficiencies of the ATP binding cassette transporters ABCA1 and ABCG1 displayed a dramatic increase in HSPC mobilization and extramedullary hematopoiesis. Increased extramedullary hematopoiesis was associated with elevated serum levels of G-CSF due to generation of IL-23 by splenic macrophages and dendritic cells. This favored hematopoietic lineage decisions toward granulocytes rather than macrophages in the bone marrow leading to impaired support for osteoblasts and decreased Cxcl12/SDF-1 production by mesenchymal progenitors. Greater HSPC mobilization and extramedullary hematopoiesis were reversed by raising HDL levels in Abca1(-/-)Abcg1(-/-) and Apoe(-/-) mice or in a mouse model of myeloproliferative neoplasm mediated by Flt3-ITD mutation. Our data identify a role of cholesterol efflux pathways in the control of HSPC mobilization. This may translate into therapeutic strategies for atherosclerosis and hematologic malignancies.
Copyright © 2012 Elsevier Inc. All rights reserved.

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Year:  2012        PMID： 22862945      PMCID： PMC3413200          DOI： 10.1016/j.stem.2012.04.024

Source DB:  PubMed          Journal:  Cell Stem Cell        ISSN： 1875-9777            Impact factor:   24.633


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