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
リソース情報
ヒト・動物細胞 MC3T3-E1(RCB1126) OP9(RCB1124)