Ayako Nakamura-Ishizu
Department School of Medicine, School of Medicine Position Professor and Division head |
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Article types | Original article |
Language | English |
Peer review | Peer reviewed |
Presence of invitation | Invited paper |
Title | Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. |
Journal | Formal name:Blood Abbreviation:Blood ISSN code:15280020/00064971 |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 119(23),pp.5429-37 |
Author and coauthor | Nakamura-Ishizu Ayako, Okuno Yuji, Omatsu Yoshiki, Okabe Keisuke, Morimoto Junko, Uede Toshimitsu, Nagasawa Takashi, Suda Toshio, Kubota Yoshiaki |
Publication date | 2012/06 |
Summary | 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 |