The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche.
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.
Omatsu
Yoshiki
Y
Department of Immunobiology and Hematology, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
Sugiyama
Tatsuki
T
Kohara
Hiroshi
H
Kondoh
Gen
G
Fujii
Nobutaka
N
Kohno
Kenji
K
Nagasawa
Takashi
T
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*
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