title: The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche.
abstract: Hematopoietic stem cells (HSCs) and their lympho-hematopoietic progeny are supported by microenvironmental niches within bone marrow; however, the identity, nature, and function of these niches remain unclear. Short-term ablation of CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells in vivo did not affect the candidate niches, bone-lining osteoblasts, or endothelial cells but severely impaired the adipogenic and osteogenic differentiation potential of marrow cells and production of the cytokines SCF and CXCL12 and led to a marked reduction in cycling lymphoid and erythroid progenitors. HSCs from CAR cell-depleted mice were reduced in number and cell size, were more quiescent, and had increased expression of early myeloid selector genes, similar to the phenotype of wild-type HSCs cultured without a niche. Thus, the niche composed of adipo-osteogenic progenitors is required for proliferation of HSCs and lymphoid and erythroid progenitors, as well as maintenance of HSCs in an undifferentiated state.
authors.affiliation: Department of Immunobiology and Hematology, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Omatsu
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kohara
authors.forename: Gen
authors.initials: G
authors.lastname: Kondoh
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Kenji
authors.initials: K
authors.lastname: Kohno
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagasawa
mesh_terms: D017667:Adipocytes / Q000166:cytology; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000502:physiology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis; D019089:Stem Cell Factor / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D019089:Stem Cell Factor