Differential cytokine contributions of perivascular haematopoietic stem cell niches

Noboru Asada, Yuya Kunisaki, Halley Pierce, Zichen Wang, Nicolas F. Fernandez, Alexander Birbrair, Avi Ma'ayan, Paul S. Frenette

Research output: Contribution to journalArticle

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Abstract

Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs. Selective Cxcl12 deletion from arteriolar NG2+ cells, but not from sinusoidal LepR+ cells, caused HSC reductions and altered HSC localization in BM. By contrast, deletion of Scf in LepR+ cells, but not NG2+ cells, led to reductions in BM HSC numbers. These results uncover distinct contributions of cytokines derived from perivascular cells in separate vascular niches to HSC maintenance.

Original languageEnglish
Pages (from-to)214-223
Number of pages10
JournalNature Cell Biology
Volume19
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

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Stem Cell Niche
Hematopoietic Stem Cells
Cytokines
Leptin Receptors
Neuroglia
Stem Cell Factor
Bone Marrow
Chemokine CXCL12
Antigens
Nestin
Antigen Receptors
Arterioles
Mesenchymal Stromal Cells
Blood Vessels
Cell Count
Maintenance
Ligands
Neurons

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Asada, N., Kunisaki, Y., Pierce, H., Wang, Z., Fernandez, N. F., Birbrair, A., ... Frenette, P. S. (2017). Differential cytokine contributions of perivascular haematopoietic stem cell niches. Nature Cell Biology, 19(3), 214-223. https://doi.org/10.1038/ncb3475

Differential cytokine contributions of perivascular haematopoietic stem cell niches. / Asada, Noboru; Kunisaki, Yuya; Pierce, Halley; Wang, Zichen; Fernandez, Nicolas F.; Birbrair, Alexander; Ma'ayan, Avi; Frenette, Paul S.

In: Nature Cell Biology, Vol. 19, No. 3, 01.03.2017, p. 214-223.

Research output: Contribution to journalArticle

Asada, N, Kunisaki, Y, Pierce, H, Wang, Z, Fernandez, NF, Birbrair, A, Ma'ayan, A & Frenette, PS 2017, 'Differential cytokine contributions of perivascular haematopoietic stem cell niches', Nature Cell Biology, vol. 19, no. 3, pp. 214-223. https://doi.org/10.1038/ncb3475
Asada, Noboru ; Kunisaki, Yuya ; Pierce, Halley ; Wang, Zichen ; Fernandez, Nicolas F. ; Birbrair, Alexander ; Ma'ayan, Avi ; Frenette, Paul S. / Differential cytokine contributions of perivascular haematopoietic stem cell niches. In: Nature Cell Biology. 2017 ; Vol. 19, No. 3. pp. 214-223.
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