Distinct vascular niches determine hematopoietic stem cell fate

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Abstract

Identification of cellular constituents of the hematopoietic stem cell (HSC) niche has recently been the subject of intensive investigation. To investigate the spatial localization of the HSC niches in bone marrow, we have established a whole-mount immunofluorescence imaging technique in which the 3D spatial relationships between stromal structures and HSCs in the BM can be precisely determined. The imaging assessment combined with computational simulations has uncovered a significant association between HSCs and arterioles, ensheathed exclusively by rare Nestin(bright) NG2⁺ pericytes (Nes(peri) cells), distinct from sinusoid-associated Nestin(dim) Leptin receptor (LepR)⁺ (Nes(retic)) cells which reportedly represent peri-vascular niche cells. Depletion of NG2⁺ cells using NG2-creERTM / inducible diphtheria toxin receptor (iDTR) mice changed HSC localization away from arterioles, induced HSC cycling and reduced long-term repopulation of HSCs in BM, suggesting that periarteriolar NG2⁺ cells form quiescent niches for HSCs. These results form the basis of studies that will allow us to genetically dissect the functions of distinct vascular niches. This vascular niche model, in which arterioles and sinusoids differentially regulate HSC quiescence and proliferation, respectively, have implications for the behavior of healthy HSC and may be useful in the future for evaluating the niches for cancer (leukemic) stem cells.

Original languageEnglish
Pages (from-to)606-613
Number of pages8
Journal[Rinshō ketsueki] The Japanese journal of clinical hematology
Volume56
Issue number6
DOIs
Publication statusPublished - Jun 1 2015

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Hematopoietic Stem Cells
Blood Vessels
Arterioles
Stem Cell Niche
Nestin
Pericytes
Leptin Receptors
Neoplastic Stem Cells
Fluorescent Antibody Technique
Bone Marrow
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Distinct vascular niches determine hematopoietic stem cell fate. / Kunisaki, Yuya.

In: [Rinshō ketsueki] The Japanese journal of clinical hematology, Vol. 56, No. 6, 01.06.2015, p. 606-613.

Research output: Contribution to journalArticle

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