Identification of mesenchymal stem cell (MSC)‐transcription factors by microarray and knockdown analyses, and signature molecule‐marked MSC in bone marrow by immunohistochemistry

Genes to Cells - Tập 14 Số 3 - Trang 407-424 - 2009
Hiroshi Kubo1, Masakazu Shimizu1, Yuji Taya2, Takeshi Kawamoto1, Masahiko Michida3, Emi Kaneko1, Akira Igarashi1, Masahiro Nishimura4, Kazumi Segoshi4, Yoshihito Shimazu2, Koichiro Tsuji5, Takaaki Aoba2, Yukio Kato1
1Department of Dental and Medical Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
2Department of Pathology, Nippon Dental University, Tokyo, Japan
3Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical & Sciences, Hiroshima University, Hiroshima, Japan
4Prosthetic Dentistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
5Two Cells Co. Ltd. Hiroshima, Japan

Tóm tắt

Althoughex vivoexpanded mesenchymal stem cells (MSC) have been used in numerous studies, the molecular signature andin vivodistribution 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 markersin vitroandin vivo, and that MSC‐characteristic transcription factors are involved in MSC stemness regulation.

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Genes to Cells

Tập 14 Số 3

407-424

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