論文 - 詳細
| RRC ID | 17573 |
|---|---|
| 著者 | Nakamura-Ishizu A, Okuno Y, Omatsu Y, Okabe K, Morimoto J, Uede T, Nagasawa T, Suda T, Kubota Y. |
| タイトル | Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. |
| ジャーナル | Blood |
| Abstract |
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. |
| 巻・号 | 119(23) |
| ページ | 5429-37 |
| 公開日 | 2012-6-7 |
| DOI | 10.1182/blood-2011-11-393645 |
| PII | S0006-4971(20)47729-8 |
| PMID | 22553313 |
| PMC | PMC3418770 |
| MeSH | Animals Bone Marrow / drug effects Bone Marrow / metabolism* Bone Marrow / radiation effects Bone Marrow Cells / cytology* Bone Marrow Cells / metabolism Bone Marrow Transplantation Cell Proliferation Endothelial Cells / cytology Endothelial Cells / metabolism Fluorouracil / administration & dosage Fluorouracil / adverse effects Gene Deletion Hematopoiesis* Hematopoietic Stem Cells / cytology* Hematopoietic Stem Cells / metabolism Integrin alpha Chains / genetics Mice Mice, Inbred C57BL RNA, Messenger / genetics Stromal Cells / cytology Stromal Cells / metabolism Tenascin / analysis Tenascin / genetics Tenascin / metabolism* Up-Regulation Whole-Body Irradiation |
| IF | 17.794 |
| 引用数 | 80 |
| WOS 分野 | HEMATOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00169 |