イシズ　アヤコ   Ishizu Ayako   石津　綾子    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
招待の有無	招待あり
表題	Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration.
掲載誌名	正式名：Blood 略　 称：Blood ISSNコード：15280020/00064971
掲載区分	国外
巻・号・頁	119(23),pp.5429-37
著者・共著者	Nakamura-Ishizu Ayako, Okuno Yuji, Omatsu Yoshiki, Okabe Keisuke, Morimoto Junko, Uede Toshimitsu, Nagasawa Takashi, Suda Toshio, Kubota Yoshiaki
発行年月	2012/06
概要	The BM microenvironment is required for the maintenance, proliferation, and mobilization of hematopoietic stem and progenitor cells (HSPCs), both during steady-state conditions and hematopoietic recovery after myeloablation. The ECM meshwork has long been recognized as a major anatomical component of the BM microenvironment; however, the molecular signatures and functions of the ECM to support HSPCs are poorly understood. Of the many ECM proteins, the expression of tenascin-C (TN-C) was found to be dramatically up-regulated during hematopoietic recovery after myeloablation. The TN-C gene was predominantly expressed in stromal cells and endothelial cells, known as BM niche cells, supporting the function of HSPCs. Mice lacking TN-C (TN-C(-/-)) mice showed normal steady-state hematopoiesis; however, they failed to reconstitute hematopoiesis after BM ablation and showed high lethality. The capacity to support transplanted wild-type hematopoietic cells to regenerate hematopoiesis was reduced in TN-C(-/-) recipient mice. In vitro culture on a TN-C substratum promoted the proliferation of HSPCs in an integrin α9-dependent manner and up-regulated the expression of the cyclins (cyclinD1 and cyclinE1) and down-regulated the expression of the cyclin-dependent kinase inhibitors (p57(Kip2), p21(Cip1), p16(Ink4a)). These results identify TN-C as a critical component of the BM microenvironment that is required for hematopoietic regeneration.
DOI	10.1182/blood-2011-11-393645
PMID	22553313