Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/61480
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Type: Journal article
Title: Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches
Author: Winkler, I.
Barbier, V.
Wadley, R.
Zannettino, A.
Williams, S.
Levesque, J.
Citation: Blood, 2010; 116(3):375-385
Publisher: Amer Soc Hematology
Issue Date: 2010
ISSN: 0006-4971
1528-0020
Statement of
Responsibility: 
Ingrid G. Winkler, Valérie Barbier, Robert Wadley, Andrew C. W. Zannettino, Sharon Williams and Jean-Pierre Lévesque
Abstract: Hematopoietic stem cell (HSC) niches have been reported at the endosteum or adjacent to bone marrow (BM) vasculature. To investigate functional attributes of these niches, mice were perfused with Hoechst 33342 (Ho) in vivo before BM cell collection in presence of pump inhibitors and antibody stained. We report that the position of phenotypic HSCs, multipotent and myeloid progenitors relative to blood flow, follows a hierarchy reflecting differentiation stage, whereas mesenchymal stromal cells are perivascular. Furthermore, during granulocyte colony-stimulating factor-induced mobilization, HSCs migrated closer to blood flow, whereas stromal cells did not. Interestingly, phenotypic Lin(-)Sca1(+)KIT(+)CD41(-)CD48(-)CD150(+) HSCs segregated into 2 groups (Ho(neg) or Ho(med)), based on degree of blood/Ho perfusion of their niche. HSCs capable of serial transplantation and long-term bromodeoxyuridine label retention were enriched in Ho(neg) HSCs, whereas Ho(med) HSCs cycled more frequently and only reconstituted a single host. This suggests that the most potent HSC niches are enriched in locally secreted factors and low oxygen tension due to negligible blood flow. Importantly, blood perfusion of niches correlates better with HSC function than absolute distance from vasculature. This technique enables prospective isolation of serially reconstituting HSCs distinct from other less potent HSCs of the same phenotype, based on the in vivo niche in which they reside.
Keywords: Bone Marrow Cells
Hematopoietic Stem Cells
Myeloid Progenitor Cells
Stromal Cells
Multipotent Stem Cells
Bone Marrow
Animals
Mice, Congenic
Mice, Inbred C57BL
Mice
Benzimidazoles
Granulocyte Colony-Stimulating Factor
Recombinant Proteins
Bromodeoxyuridine
Fluorescent Dyes
Blood Flow Velocity
Hematopoietic Stem Cell Mobilization
Cell Differentiation
Cell Hypoxia
Phenotype
Rights: Copyright © 2010 by American Society of Hematology
DOI: 10.1182/blood-2009-07-233437
Grant ID: http://purl.org/au-research/grants/nhmrc/288701
http://purl.org/au-research/grants/nhmrc/434515
Published version: http://dx.doi.org/10.1182/blood-2009-07-233437
Appears in Collections:Aurora harvest
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