Molecular signatures of quiescent, mobilized and leukemia-initiating hematopoietic stem cells.

PloS One
E Camilla ForsbergIrving L Weissman

Abstract

Hematopoietic stem cells (HSC) are rare, multipotent cells capable of generating all specialized cells of the blood system. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecular pathways controlling stem cell quiescence remain poorly characterized. Likewise, the molecular events driving leukemogenesis remain elusive. In this study, we compare the gene expression profiles of steady-state bone marrow HSC to non-self-renewing multipotent progenitors; to HSC treated with mobilizing drugs that expand the HSC pool and induce egress from the marrow; and to leukemic HSC in a mouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances, and thus may be particularly important for the maintenance and function of normal, quiescent HSC. These results identify potential key regulators of HSC and give insights into the clinically important processes of HSC mobilization for transplantation and leukemic development from cancer stem cells.

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Citations

Apr 7, 2010·Cell Stem Cell·Daniel Goff, Catriona Jamieson
Mar 2, 2013·Cell Death and Differentiation·D Dolfini, R Mantovani
Aug 10, 2012·Journal of Biological Dynamics·Shinji Nakaoka, Kazuyuki Aihara
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Aug 13, 2013·PloS One·Corinna MontroneAndreas Ruepp
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Nov 15, 2018·Frontiers in Cell and Developmental Biology·Masahiro Marshall NakagawaChozha Vendan Rathinam

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Methods Mentioned

BETA
GTPase
FACS

Software Mentioned

SAM
BLAST
Statistical Analysis of Microarrays ( SAM )
Significance Analysis of Microarrays ( SAM

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