Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: Serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches

Winkler, Ingrid G., Barbier, Valérie, Wadley, Robert, Zannettino, Andrew C. W., Williams, Sharon and Lévesque, Jean-Pierre (2010) Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: Serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches. Blood, 116 3: 375-385. doi:10.1182/blood-2009-07-233437


Author Winkler, Ingrid G.
Barbier, Valérie
Wadley, Robert
Zannettino, Andrew C. W.
Williams, Sharon
Lévesque, Jean-Pierre
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
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2010-07-22
Sub-type Article (original research)
DOI 10.1182/blood-2009-07-233437
Open Access Status
Volume 116
Issue 3
Start page 375
End page 385
Total pages 11
Editor Cynthia E. Dunbar
Place of publication Washington, DC, U.S.A.
Publisher American Society of Hematology
Collection year 2011
Language eng
Formatted 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 LinSca1+KIT+ CD41CD48CD150+ HSCs segregated into 2 groups (Honeg or Homed), based on degree of blood/Ho perfusion of their niche. HSCs capable of serial transplantation and longterm bromodeoxyuridine label retention were enriched inHoneg HSCs, whereas Homed 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. 
Keyword Colony-stimulating factor
Progenitor cells
Self-renewal
Mobilization
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Faculty of Health and Behavioural Sciences -- Publications
Official 2011 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 112 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 123 times in Scopus Article | Citations
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Created: Sun, 15 Aug 2010, 00:07:01 EST