title: Membrane channel connexin 32 maintains Lin(-)/c-kit(+) hematopoietic progenitor cell compartment: analysis of the cell cycle.
abstract: Membrane channel connexin (Cx) forms gap junctions that are implicated in the homeostatic regulation of multicellular systems; thus, hematopoietic cells were assumed not to express Cxs. However, hematopoietic progenitors organize a multicellular system during the primitive stage; thus, the aim of the present study was to determine whether Cx32, a member of the Cx family, may function during the primitive steady-state hematopoiesis in the bone marrow (BM). First, the numbers of mononuclear cells in the peripheral blood and various hematopoietic progenitor compartments in the BM decreased in Cx32-knockout (KO) mice. Second, on the contrary, the number of primitive hematopoietic progenitor cells, specifically the Lin(-)/c-kit(+)/Scal(+ )fraction, the KSL progenitor cell compartment, also increased in Cx32-KO mice. Third, expression of Cx32 was detected in Lin(-)/c-kit(+) hematopoietic progenitor cells of wild-type mice (0.27% in the BM), whereas it was not detected in unfractionated wild-type BM cells. Furthermore, cell-cycle analysis of the fractionated KSL compartment from Cx32-KO BM showed a higher ratio in the G(2)/M fraction. Taken together, all these results imply that Cx32 is expressed solely in the primitive stem cell compartment, which maintains the stemness of the cells, i.e., being quiescent and noncycling; and once Cx32 is knocked out, these progenitor cells are expected to enter the cell cycle, followed by proliferation and differentiation for maintaining the number of peripheral blood cells.
authors.affiliation: Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences, Tokyo, Japan. yokohira@nihs.go.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Byung-Il
authors.initials: BI
authors.lastname: Yoon
authors.forename: Isao
authors.initials: I
authors.lastname: Tsuboi
authors.forename: Yan
authors.initials: Y
authors.lastname: Huo
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kodama
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Thomas
authors.initials: T
authors.lastname: Ott
authors.forename: James E
authors.initials: JE
authors.lastname: Trosko
authors.forename: Tohru
authors.initials: T
authors.lastname: Inoue
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D017630:Connexins / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D007473:Ion Channels / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009713:Nucleotidyltransferases / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D007473:Ion Channels; D009713:Nucleotidyltransferases; D019009:Proto-Oncogene Proteins c-kit; D000097002:Gap Junction beta-1 Protein; C057535:lincosaminide O-nucleotidyltransferase