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Science 328 (5986): 1689-1693

Copyright © 2010 by the American Association for the Advancement of Science

ATP-Binding Cassette Transporters and HDL Suppress Hematopoietic Stem Cell Proliferation

Laurent Yvan-Charvet,1,*,{dagger} Tamara Pagler,1,* Emmanuel L. Gautier,2 Serine Avagyan,2 Read L. Siry,1 Seongah Han,1 Carrie L. Welch,1 Nan Wang,1 Gwendalyn J. Randolph,2 Hans W. Snoeck,2 Alan R. Tall1

Abstract: Elevated leukocyte cell numbers (leukocytosis), and monocytes in particular, promote atherosclerosis; however, how they become increased is poorly understood. Mice deficient in the adenosine triphosphate–binding cassette (ABC) transporters ABCA1 and ABCG1, which promote cholesterol efflux from macrophages and suppress atherosclerosis in hypercholesterolemic mice, displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell population containing LinSca-1+Kit+ (LSK) in the bone marrow. Transplantation of Abca1–/– Abcg1–/– bone marrow into apolipoprotein A-1 transgenic mice with elevated levels of high-density lipoprotein (HDL) suppressed the LSK population, reduced leukocytosis, reversed the myeloproliferative disorder, and accelerated atherosclerosis. The findings indicate that ABCA1, ABCG1, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis.

1 Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA.
2 Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ly2159{at}columbia.edu


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