TY - JOUR
T1 - Differential cytokine contributions of perivascular haematopoietic stem cell niches
AU - Asada, Noboru
AU - Kunisaki, Yuya
AU - Pierce, Halley
AU - Wang, Zichen
AU - Fernandez, Nicolas F.
AU - Birbrair, Alexander
AU - Ma'ayan, Avi
AU - Frenette, Paul S.
N1 - Funding Information:
We thank C. Prophete, P. Ciero and C. Cruz for technical assistance and L. Tesfa, Y. Wang and D. Sun for helpwith cell sorting.We thank T.Nagasawa and S.Morrison for providing reagents. This work was supported by R01 grants from the National Institutes of Health (NIH) (DK056638, HL116340, HL097819 to P.S.F.), New York Stem Cell Foundation and NIH's Common Fund (U54HL127624, U54CA189201 to A.M.).We are also grateful to the New York State Department of Health (NYSTEM Program) for shared facility (C029154) and research support (N13G-262) and the Leukaemia and Lymphoma Society's Translational Research Program. Y.K. is supported by JSPS Grant-in Aid for Scientific Research (B)(15H04859) and the Takeda Science Foundation. N.A. is supported by JSPS Postdoctoral Fellowships for Research Abroad.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85014219397&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014219397&partnerID=8YFLogxK
U2 - 10.1038/ncb3475
DO - 10.1038/ncb3475
M3 - Article
C2 - 28218906
AN - SCOPUS:85014219397
VL - 19
SP - 214
EP - 223
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 3
ER -