title: Identification of mesenchymal stem cell (MSC)-transcription factors by microarray and knockdown analyses, and signature molecule-marked MSC in bone marrow by immunohistochemistry.
abstract: Although ex vivo expanded mesenchymal stem cells (MSC) have been used in numerous studies, the molecular signature and in vivo distribution status of MSC remain unknown. To address this matter, we identified numerous human MSC-characteristic genes--including nine transcription factor genes--using DNA microarray and real-time RT-PCR analyses: Most of the MSC-characteristic genes were down-regulated 24 h after incubation with osteogenesis-, chondrogenesis- or adipogenesis-induction medium, or 48-72 h after knockdown of the nine transcription factors. Furthermore, knockdowns of ETV1, ETV5, FOXP1, GATA6, HMGA2, SIM2 or SOX11 suppressed the self-renewal capacity of MSC, whereas those of FOXP1, SOX11, ETV1, SIM2 or PRDM16 reduced the osteogenic- and/or adipogenic potential. In addition, immunohistochemistry using antibodies for the MSC characteristic molecules--including GATA6, TRPC4, FLG and TGM2--revealed that MSC-like cells were present near the endosteum and in the interior of bone marrow of adult mice. These findings indicate that MSC synthesize a set of MSC markers in vitro and in vivo, and that MSC-characteristic transcription factors are involved in MSC stemness regulation.
authors.affiliation: Department of Dental and Medical Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shimizu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Michida
authors.forename: Emi
authors.initials: E
authors.lastname: Kaneko
authors.forename: Akira
authors.initials: A
authors.lastname: Igarashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishimura
authors.forename: Kazumi
authors.initials: K
authors.lastname: Segoshi
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Shimazu
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuji
authors.forename: Takaaki
authors.initials: T
authors.lastname: Aoba
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
mesh_terms: D005347:Fibroblasts / Q000166:cytology; D000091344:Filaggrin Proteins; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012867:Skin / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D014157:Transcription Factors