title: Differential cytokine contributions of perivascular haematopoietic stem cell niches.
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.
authors.affiliation: Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA.|Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Noboru
authors.initials: N
authors.lastname: Asada
authors.affiliation: Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA.|Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kunisaki
authors.affiliation: Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA.|Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Halley
authors.initials: H
authors.lastname: Pierce
authors.affiliation: Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Zichen
authors.identifier: 0000-0002-1415-1286
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Fernandez
authors.affiliation: Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA.|Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Alexander
authors.identifier: 0000-0003-1015-2561
authors.initials: A
authors.lastname: Birbrair
authors.affiliation: Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Avi
authors.identifier: 0000-0002-6904-1017
authors.initials: A
authors.lastname: Ma'ayan
authors.affiliation: Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York 10461, USA.|Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.|Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
mesh_terms: D000818:Animals; D000941:Antigens; D001160:Arterioles / Q000166:cytology; D001853:Bone Marrow / Q000378:metabolism; D002452:Cell Count; D054377:Chemokine CXCL12 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D021621:Imaging, Three-Dimensional; D019426:Integrases / Q000378:metabolism; D008822:Mice, Transgenic; D064231:Nestin / Q000378:metabolism; D011509:Proteoglycans; D054411:Receptors, Leptin / Q000378:metabolism; D017423:Sequence Analysis, RNA; D019089:Stem Cell Factor / Q000378:metabolism; D055153:Stem Cell Niche; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D054377:Chemokine CXCL12; D016207:Cytokines; D049452:Green Fluorescent Proteins; D019426:Integrases; D064231:Nestin; D011509:Proteoglycans; D054411:Receptors, Leptin; D019089:Stem Cell Factor; D000099216:Chondroitin Sulfate Proteoglycan 4; C045073:Cre recombinase