Regulation of Hematopoietic Stem and Progenitor Cell Mobilization by Cholesterol Efflux Pathways

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Aug 7

PMID 22862945

Citations 135

Authors

Marit Westerterp

Samuel Gourion-Arsiquaud

Andrew J Murphy

Alan Shih

Serge Cremers

Ross L Levine

Alan R Tall

Laurent Yvan-Charvet

Affiliations

Soon will be listed here.

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.

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