Stress hematopoiesis regualted by C/EBPbeta transcription factor
| Project/Area Number |
18K08354
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 54010:Hematology and medical oncology-related
|
|---|
| Research Institution | Tokyo University of Pharmacy and Life Science (2020-2021)
Kyoto University (2018-2019) |
|---|
Principal Investigator |
HIRAI HIDEYO 東京薬科大学, 生命科学部, 教授 (50315933)
|
|---|
| Project Period (FY) |
2018-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 造血幹細胞 / 生体防御 / 分化 / 転写因子 / ストレス造血 / C/EBPβ / 増殖 / 転写制御 |
|---|
| Outline of Final Research Achievements |
The transcription factor C/EBPβ is required for stress-induced granulopoiesis which requires both proliferation and differentiation of hematopoietic stem/progenitor cells (HSPCs). In this study, we focused on the three isoforms of C/EBPβ. Under stress conditions, Cebpb-/- HSPCs exhibited impaired cell cycle activation and myeloid differentiation at the early and late phases of regeneration, respectively. Novel flow cytometric analysis revealed that among the three isoforms of C/EBPβ, LIP was upregulated in HSCs prior to LAP/LAP* during regeneration. Early upregulation of LIP promoted cell cycle entry of HSCs and expanded HSPCs pool. Subsequent myeloid differentiation of amplified HSPCs was mediated by LAP/LAP*, which were upregulated at a later phase of regeneration. Collectively, our findings show that stress-induced sequential upregulation of C/EBPβ isoforms is critical for fine-tuning the proliferation and differentiation of regenerating HSPCs.
|
| Academic Significance and Societal Importance of the Research Achievements |
今回の研究で、転写因子C/EBPβのアイソフォームの発現を単一細胞レベルで解析できる実験系の確立とともに、骨髄球系細胞の増殖と分化の両方が必要とされるストレス負荷時の造血幹細胞制御におけるC/EBPβの作用メカニズムの一端をはじめて明らかにすることができた。今後、個々のアイソフォームが欠損するようなマウスの解析などによって知見を集積し、ストレス造血の制御機構の全貌解明と、それが破綻した状態としての造血器悪性腫瘍の病態解明、体外での骨髄球系細胞の産生と細胞療法への応用などへの展開が考えられる。
|
Report
(5 results)
Research Products
(36 results)
-
-
-
-
-
-
-
[Journal Article] Successful granulocyte apheresis using medium molecular weight hydroxyethyl starch2019
Author(s)
Nanya M, Yurugi K, Kato I, Hiramatsu H, Kawabata H, Kondo T, Iemura T, Hishida R, Shibutani E, Matsui K, Nakagawa Y, Niwa N, Kasai Y, Roig JM, Arai Y, Miura Y, Takaori-Kondo A, Maekawa T and Hirai H
-
Journal Title
Int J Hematol
Volume: 110
Issue: 6
Pages: 729-735
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
[Journal Article] Loss of SMAD4 Promotes Colorectal Cancer Progression by Recruiting Tumor-Associated Neutrophils via the CXCL1/8-CXCR2 Axis.2019
Author(s)
Ogawa R, Yamamoto T, Hirai H, Hanada K, Kiyasu Y, Nishikawa G, Mizuno R, Inamoto S, Itatani Y, Sakai Y, Kawada K.
-
Journal Title
Clinical Cancer Research
Volume: －
Issue: 9
Pages: 2887-2899
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] C/EBPβ is a critical mediator of IFNα-induced exhaustion of chronic myeloid leukemia stem cells.2019
Author(s)
Yokota A, Hirai H, Sato R, Adachi H, Sato F, Hayashi Y, Sato A, Kamino N, Miura Y, Nakano M, Tenen DG, Kimura S, Tashiro K, Maekawa T
-
Journal Title
Blood Advances
Volume: 3
Issue: 3
Pages: 476-488
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Impact of Hypothermia on Differentiation and Maturation of Neutrophils.2018
Author(s)
Torikoshi Y, Shime N, Yokota A, Kamio N, Sato A, Shoji T, Kashiwagi T, Miura Y, Maekawa T, Hirai H
Organizer
American Society of Hematology, 60th Annual Meeting and Exposition
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
[Presentation] 生体肝臓移植が施行された胆道閉鎖症の乳幼児に検出された母親に対するHLA 抗体の検討.2018
Author(s)
万木紀美子, 岡島英明, 吉澤 淳, 菱田理恵, 小川絵里, 岡本竜弥, 金城昌克, 澁谷江里香, 三浦康生, 上本伸二, 前川 平, 平位秀世
Organizer
第27回 日本組織適合性学会大会
Related Report
-
-
-
-
-
-
