| RRC ID |
19200
|
| Author |
Sumitomo A, Ishino R, Urahama N, Inoue K, Yonezawa K, Hasegawa N, Horie O, Matsuoka H, Kondo T, Roeder RG, Ito M.
|
| Title |
The transcriptional mediator subunit MED1/TRAP220 in stromal cells is involved in hematopoietic stem/progenitor cell support through osteopontin expression.
|
| Journal |
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.
|
| Volume |
30(20)
|
| Pages |
4818-27
|
| Published |
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
|
| Times Cited |
16
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
MC3T3-E1(RCB1126)
OP9(RCB1124) |
