論文 - 詳細
| RRC ID | 19200 |
|---|---|
| 著者 | Sumitomo A, Ishino R, Urahama N, Inoue K, Yonezawa K, Hasegawa N, Horie O, Matsuoka H, Kondo T, Roeder RG, Ito M. |
| タイトル | The transcriptional mediator subunit MED1/TRAP220 in stromal cells is involved in hematopoietic stem/progenitor cell support through osteopontin expression. |
| ジャーナル | Mol Cell Biol |
| Abstract |
MED1/TRAP220, a subunit of the transcriptional Mediator/TRAP complex, is crucial for various biological events through its interaction with distinct activators, such as nuclear receptors and GATA family activators. In hematopoiesis, MED1 plays a pivotal role in optimal nuclear receptor-mediated myelomonopoiesis and GATA-1-induced erythropoiesis. In this study, we present evidence that MED1 in stromal cells is involved in supporting hematopoietic stem and/or progenitor cells (HSPCs) through osteopontin (OPN) expression. We found that the proliferation of bone marrow (BM) cells cocultured with MED1 knockout (Med1(-/-)) mouse embryonic fibroblasts (MEFs) was significantly suppressed compared to the control. Furthermore, the number of long-term culture-initiating cells (LTC-ICs) was attenuated for BM cells cocultured with Med1(-/-) MEFs. The vitamin D receptor (VDR)- and Runx2-mediated expression of OPN, as well as Mediator recruitment to the Opn promoter, was specifically attenuated in the Med1(-/-) MEFs. Addition of OPN to these MEFs restored the growth of cocultured BM cells and the number of LTC-ICs, both of which were attenuated by the addition of the anti-OPN antibody to Med1(+/+) MEFs and to BM stromal cells. Consequently, MED1 in niche appears to play an important role in supporting HSPCs by upregulating VDR- and Runx2-mediated transcription on the Opn promoter. |
| 巻・号 | 30(20) |
| ページ | 4818-27 |
| 公開日 | 2010-10-1 |
| DOI | 10.1128/MCB.01348-09 |
| PII | MCB.01348-09 |
| PMID | 20713445 |
| PMC | PMC2950551 |
| MeSH | Animals Coculture Techniques Core Binding Factor Alpha 1 Subunit / metabolism Hematopoietic Stem Cells / cytology Hematopoietic Stem Cells / metabolism* Humans Mediator Complex Subunit 1 / deficiency Mediator Complex Subunit 1 / genetics* Mediator Complex Subunit 1 / metabolism* Mice Mice, Knockout Osteopontin / deficiency Osteopontin / genetics* Osteopontin / metabolism* Promoter Regions, Genetic RNA, Messenger / genetics RNA, Messenger / metabolism Receptors, Calcitriol / metabolism Recombinant Proteins / genetics Recombinant Proteins / metabolism Signal Transduction Stromal Cells / cytology Stromal Cells / metabolism* Transfection Two-Hybrid System Techniques |
| IF | 3.611 |
| 引用数 | 16 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | MC3T3-E1(RCB1126) OP9(RCB1124) |