title: Low level of c-kit expression marks deeply quiescent murine hematopoietic stem cells.
abstract: Although c-kit is expressed highly on murine hematopoietic stem cells (HSCs) and essential for bone marrow (BM) hematopoiesis, the significance of the high level of expression of c-kit on HSCs was not well determined. We show here that CD150(+) CD48(-) Lineage(-) Sca-1(+) c-kit(+) HSCs in adult BM are distributed within the range of roughly a 20-fold difference in the expression level of c-kit, and that c-kit density correlates with the cycling status of the HSC population. This predisposition is more evident in the BM of mice older than 30 weeks. The HSCs in G(0) phase express a lower level of c-kit both on the cell surface and inside the cells, which cannot be explained by ligand receptor binding and internalization. It is more likely that the low level of c-kit expression is a unique property of HSCs in G(0). Despite functional differences in the c-kit gradient, the HSCs are uniformly hypoxic and accessible to blood perfusion. Therefore, our data indicate the possibility that the hypoxic state of the HSCs is actively regulated, rather than them being passively hypoxic through a simple anatomical isolation from the circulation.
authors: Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Kansai Medical University, Moriguchi, Osaka, Japan.
authors: Yoshikazu
authors: Y
authors: Matsuoka
authors: Yutaka
authors: Y
authors: Sasaki
authors: Ryusuke
authors: R
authors: Nakatsuka
authors: Masaya
authors: M
authors: Takahashi
authors: Ryuji
authors: R
authors: Iwaki
authors: Yasushi
authors: Y
authors: Uemura
authors: Yoshiaki
authors: Y
authors: Sonoda
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000071178:CD48 Antigen; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; D001562:Benzimidazoles; D000071178:CD48 Antigen; C000604066:Cd48 protein, mouse; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D019009:Proto-Oncogene Proteins c-kit; C017807:bisbenzimide ethoxide trihydrochloride