Document Detail


The transcriptional mediator subunit MED1/TRAP220 in stromal cells is involved in hematopoietic stem/progenitor cell support through osteopontin expression.
MedLine Citation:
PMID:  20713445     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Akiko Sumitomo; Ruri Ishino; Norinaga Urahama; Kana Inoue; Kenji Yonezawa; Natsumi Hasegawa; Osamu Horie; Hiroshi Matsuoka; Toru Kondo; Robert G Roeder; Mitsuhiro Ito
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-16
Journal Detail:
Title:  Molecular and cellular biology     Volume:  30     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-23     Completed Date:  2010-10-28     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4818-27     Citation Subset:  IM    
Affiliation:
Division of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Coculture Techniques
Core Binding Factor Alpha 1 Subunit / metabolism
Hematopoietic Stem Cells / cytology,  metabolism*
Humans
Mediator Complex Subunit 1 / deficiency,  genetics*,  metabolism*
Mice
Mice, Knockout
Osteopontin / deficiency,  genetics*,  metabolism*
Promoter Regions, Genetic
RNA, Messenger / genetics,  metabolism
Receptors, Calcitriol / metabolism
Recombinant Proteins / genetics,  metabolism
Signal Transduction
Stromal Cells / cytology,  metabolism*
Transfection
Two-Hybrid System Techniques
Grant Support
ID/Acronym/Agency:
DK071900/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Core Binding Factor Alpha 1 Subunit; 0/MED1 protein, human; 0/Med1 protein, mouse; 0/Mediator Complex Subunit 1; 0/RNA, Messenger; 0/Receptors, Calcitriol; 0/Recombinant Proteins; 0/Runx2 protein, mouse; 0/Spp1 protein, mouse; 106441-73-0/Osteopontin
Comments/Corrections

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