Elucidation of mechanisms regulating pancreatic b-cell proliferation using single-cell epigenomic analysis
Project/Area Number |
17K19654
|
Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
Allocation Type | Multi-year Fund |
Research Field |
General internal medicine and related fields
|
Research Institution | Kyoto University |
Principal Investigator |
|
Research Collaborator |
YABE Daisuke 京都大学大学院医学研究科, 先端糖尿病学, 特定准教授
WATANABE Akira 京都大学iPS細胞研究所, 未来生命科学開拓部, 主任研究員
|
Project Period (FY) |
2017-06-30 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
|
Keywords | 膵β細胞 / 増殖 / インスリン / 老化 |
Outline of Final Research Achievements |
Mechanisms regulating pancreatic β cell mass remain largely unknown; and need to be investigated critically to invent potential therapeutics for diabetes. The current study aims to understand such mechanisms through multi-omics approaches including single-cell RNA-sequence of β cells before and after partial pancreatectomy, which induces robust β cell proliferation in young but not old mice. Our study revealed that β cells falls into 4 distinct subpopulations, one for which is characterized by expression of genes involved in cell proliferation and found only in young mice. We also found novel transcriptional factors possibly involved in β cell proliferation. In addition, we succeeded in the establishment of mice expressing the cell cycle reporter in β cells. Combined with the tissue clearing technique, we succeeded in measuring β cell proliferation in situ.
|
Academic Significance and Societal Importance of the Research Achievements |
膵β細胞量減少は糖尿病予防・治療の重要な課題であるが膵β細胞量の制御機構の全容は不明であり、膵β細胞量を標的とした糖尿病治療法は存在しない。特に加齢とともに膵β細胞が増殖能を失う分子機序については、十分な検討がなされていない。膵β細胞の増殖制御機構を解明しようとする本研究は、糖尿病の発症や重症化を阻止するための全く新しい治療戦略創出の糸口となることが期待できる。
|
Report
(3 results)
Research Products
(26 results)
-
-
-
-
-
[Journal Article] Sphingosine kinase 1-interacting protein is a dual regulator of insulin and incretin secretion2019
Author(s)
Liu Y, Harashima SI, Wang Y, Suzuki K, Tokumoto S, Usui R, Tatsuoka H, Tanaka D, Yabe D, Harada N, Hayashi Y, Inagaki N.
-
Journal Title
FASEB J.
Volume: 33
Issue: 5
Pages: 6239-6253
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
[Journal Article] Transcriptional factor Pdx1 is involved in age-related GIP hypersecretion in mice.2018
Author(s)
Ikeguchi E, Harada N, Kanemaru Y, Sankoda A, Yamane S, Iwasaki K, Imajo M, Murata Y, Suzuki K, Joo E, Inagaki N.
-
Journal Title
Am J Physiol Gastrointest Liver Physiol.
Volume: 315
Issue: 2
Pages: 272-272
DOI
Related Report
Peer Reviewed
-
[Journal Article] Glucose-dependent insulinotropic polypeptide is required for moderate high fat diet, but not high carbohydrate diet-induced weight gain.2018
Author(s)
Maekawa R, Ogata H, Murase M, Harada N, Suzuki K, Joo E, Sankoda A, Iida A, Izumoto T, Tsunekawa S, Hamada Y, Oiso Y, Inagaki N, Arima H, Hayashi Y, Seino Y.
-
Journal Title
Am J Physiol Endocrinol Metab.
Volume: 6
Issue: 6
Pages: 111-112
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] β-cell-specific overexpression of adiponectin receptor 1 does not improve diabetes mellitus in Akita mice.2018
Author(s)
Choi J, Kobayashi H, Okuda H, Harada KH, Takeda M, Fujimoto H, Yamane S, Tanaka D, Youssefian S, Inagaki N, Koizumi A.
-
Journal Title
PLoS One
Volume: 13 (1)
Issue: 1
Pages: e0190863-e0190863
DOI
NAID
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Heterozygous RFX6 protein truncating variants are associated with MODY with reduced penetrance.2017
Author(s)
Patel KA, Kettunen J, Laakso M, Stancakova; A, Laver TW, Colclough K, Johnson MB, Abramowicz M, Groop L, Miettinen PJ, Shepherd MH, Flanagan SE, Ellard S, Inagaki N, Hattersley AT, Tuomi T, Cnop M, Weedon MN.
-
Journal Title
Nat Commun
Volume: 8(1)
Issue: 1
Pages: 888-888
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Diverse metabolic effects of O-GlcNAcylation in the pancreas but limited effects in insulin-sensitive organs in mice.2017
Author(s)
Ida S, Morino K, Sekine O, Ohashi N, Kume S, Chano T, Iwasaki K, Harada N, Inagaki N, Ugi S, Maegawa H.
-
Journal Title
Diabetologia
Volume: 60 (9)
Issue: 6
Pages: 1761-1769
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-