『徳島大学 教育・研究者情報データベース (EDB)』---[学外] /
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EID=264969EID:264969, Map:0, LastModified:2015年3月20日(金) 14:45:51, Operator:[三木 ちひろ], Avail:TRUE, Censor:0, Owner:[[副研究部長]/[大学院ヘルスバイオサイエンス研究部]], Read:継承, Write:継承, Delete:継承.
種別 (必須): 学術論文 (審査論文) [継承]
言語 (必須): 英語 [継承]
招待 (推奨):
審査 (推奨): Peer Review [継承]
カテゴリ (推奨): 研究 [継承]
共著種別 (推奨):
学究種別 (推奨):
組織 (推奨):
著者 (必須): 1.石田 昌義
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
2. (英) El-Mounayri Omar (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
3. (英) Kattman Steven (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
4. (英) Zandstra Peter (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
5. (英) Sakamoto Hiroshi (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
6. (英) Ogawa Minetaro (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
7. (英) Keller Gordon (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
8. (英) Husain Mansoor (日) (読)
役割 (任意):
貢献度 (任意):
学籍番号 (推奨):
[継承]
題名 (必須): (英) Regulated expression and role of c-Myb in the cardiovascular-directed differentiation of mouse embryonic stem cells.  (日)    [継承]
副題 (任意):
要約 (任意): (英) RATIONALE:c-myb null (knockout) embryonic stem cells (ESC) can differentiate into cardiomyocytes but not contractile smooth muscle cells (SMC) in embryoid bodies (EB).OBJECTIVE:To define the role of c-Myb in SMC differentiation from ESC.METHODS AND RESULTS:In wild-type (WT) EB, high c-Myb levels on days 0-2 of differentiation undergo ubiquitin-mediated proteosomal degradation on days 2.5-3, resurging on days 4-6, without changing c-myb mRNA levels. Activin-A and bone morphogenetic protein 4-induced cardiovascular progenitors were isolated by FACS for expression of vascular endothelial growth factor receptor (VEGFR)2 and platelet-derived growth factor receptor (PDGFR). By day 3.75, hematopoesis-capable VEGFR2+ cells were fewer, whereas cardiomyocyte-directed VEGFR2+/PDGFR+ cells did not differ in abundance in knockout versus WT EB. Importantly, highest and lowest levels of c-Myb were observed in VEGFR2+ and VEGFR2+/PDGFR+ cells, respectively. Proteosome inhibitor MG132 and lentiviruses enabling inducible expression or knockdown of c-myb were used to regulate c-Myb in WT and knockout EB. These experiments showed that c-Myb promotes expression of VEGFR2 over PDGFR, with chromatin immunopreciptation and promoter-reporter assays defining specific c-Myb-responsive binding sites in the VEGFR2 promoter. Next, FACS-sorted VEGFR2+ cells expressed highest and lowest levels of SMC- and fibroblast-specific markers, respectively, at days 7-14 after retinoic acid (RA) as compared with VEGFR2+/PDGFR+ cells. By contrast, VEGFR2+/PDGFR+ cells cultured without RA beat spontaneously, like cardiomyocytes between days 7 and 14, and expressed cardiac troponin. Notably, RA was required to more fully differentiate SMC from VEGFR2+ cells and completely blocked differentiation of cardiomyocytes from VEGFR2+/PDGFR+ cells.CONCLUSIONS:c-Myb is tightly regulated by proteosomal degradation during cardiovascular-directed differentiation of ESC, expanding early-stage VEGFR2+ progenitors capable of RA-responsive SMC formation.  (日)    [継承]
キーワード (推奨): 1. (英) c-Myb (日) (読) [継承]
2. (英) Smooth muscle cells (日) (読) [継承]
3. (英) Flk-1 (日) (読) [継承]
4. (英) PDGFRa (日) (読) [継承]
5.転写因子 (transcription factor) [継承]
6.細胞増殖·分化 (cell proliferation and differentiation) [継承]
7.細胞分離 (cell separation) [継承]
8. (英) Chromatin Immunoprecipitation (日) (読) [継承]
9.プロテアソーム (proteasome) [継承]
10. (英) Embryonic Stem Cells (日) (読) [継承]
11. (英) Flow Cytometry (日) (読) [継承]
12. (英) Gene Expression Regulation, Developmental (日) (読) [継承]
13. (英) Reporter assay (日) (読) [継承]
14. (英) RNA Interference (日) (読) [継承]
15. (英) RNA, Messenger (日) (読) [継承]
16. (英) Ubiquitination (日) (読) [継承]
発行所 (推奨): American Heart Association [継承]
誌名 (必須): Circulation Research ([American Heart Association])
(pISSN: 0009-7330, eISSN: 1524-4571)

ISSN (任意): 1524-4571
ISSN: 0009-7330 (pISSN: 0009-7330, eISSN: 1524-4571)
Title: Circulation research
Title(ISO): Circ. Res.
Publisher: American Heart Association
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
[継承]
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(必須): 110 [継承]
(必須): 2 [継承]
(必須): 253 264 [継承]
都市 (任意):
年月日 (必須): 西暦 2011年 11月 23日 (平成 23年 11月 23日) [継承]
URL (任意):
DOI (任意): 10.1161/CIRCRESAHA.111.259499    (→Scopusで検索) [継承]
PMID (任意): 22116818    (→Scopusで検索) [継承]
NAID (任意):
WOS (任意): 000299432600009 [継承]
Scopus (任意): 2-s2.0-84856059943 [継承]
評価値 (任意):
被引用数 (任意):
指導教員 (推奨):
備考 (任意): 1.(英) Affiliation: Heart and Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada, M5G 1L7.  (日)    [継承]
2.(英) PublicationType: Journal Article  (日)    [継承]
3.(英) PublicationType: Research Support, Non-U.S. Gov't  (日)    [継承]

標準的な表示

和文冊子 ● Masayoshi Ishida, Omar El-Mounayri, Steven Kattman, Peter Zandstra, Hiroshi Sakamoto, Minetaro Ogawa, Gordon Keller and Mansoor Husain : Regulated expression and role of c-Myb in the cardiovascular-directed differentiation of mouse embryonic stem cells., Circulation Research, Vol.110, No.2, 253-264, 2011.
欧文冊子 ● Masayoshi Ishida, Omar El-Mounayri, Steven Kattman, Peter Zandstra, Hiroshi Sakamoto, Minetaro Ogawa, Gordon Keller and Mansoor Husain : Regulated expression and role of c-Myb in the cardiovascular-directed differentiation of mouse embryonic stem cells., Circulation Research, Vol.110, No.2, 253-264, 2011.

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