title: Endothelial and perivascular cells maintain haematopoietic stem cells.
abstract: Several cell types have been proposed to create niches for haematopoietic stem cells (HSCs). However, the expression patterns of HSC maintenance factors have not been systematically studied and no such factor has been conditionally deleted from any candidate niche cell. Thus, the cellular sources of these factors are undetermined. Stem cell factor (SCF; also known as KITL) is a key niche component that maintains HSCs. Here, using Scf(gfp) knock-in mice, we found that Scf was primarily expressed by perivascular cells throughout the bone marrow. HSC frequency and function were not affected when Scf was conditionally deleted from haematopoietic cells, osteoblasts, nestin-cre- or nestin-creER-expressing cells. However, HSCs were depleted from bone marrow when Scf was deleted from endothelial cells or leptin receptor (Lepr)-expressing perivascular stromal cells. Most HSCs were lost when Scf was deleted from both endothelial and Lepr-expressing perivascular cells. Thus, HSCs reside in a perivascular niche in which multiple cell types express factors that promote HSC maintenance.
authors.affiliation: Howard Hughes Medical Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Ding
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Saunders
authors.forename: Grigori
authors.initials: G
authors.lastname: Enikolopov
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
mesh_terms: D000483:Alleles; D000818:Animals; D004727:Endothelium / Q000166:cytology* / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D019089:Stem Cell Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D055153:Stem Cell Niche / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D054411:Receptors, Leptin; D019089:Stem Cell Factor