Regenerative mechanisms of pancreatic endocrine and exocrine cells

• Project/Area Number: 15H04812
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: KO SHIGERU 慶應義塾大学, 医学部(信濃町), 准教授 (90402578)
• Co-Investigator(Kenkyū-buntansha): 石黒 啓一郎 熊本大学, 発生医学研究所, 准教授 (30508114) ; 竹田 直樹 熊本大学, 生命資源研究・支援センター, 助教 (90304998)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: 膵内外分泌細胞 / 細胞分化誘導 / ヒトES細胞 / ベータ細胞 / 細胞分化 / 内分泌細胞 / Glp1受容体 / ノックインマウス / 膵再生分子機構 / 内外分泌細胞 / Glp-1受容体 / 膵前駆細胞

Outline of Final Research Achievements

The aim of this study was to develop GLP1 receptor knock-in mice and to develop a method for inducing β cell differentiation from human pluripotent stem cells.Recombination vector was introduced into mouse ES cells to establish genetically modified mice. Pancreatic endocrine cells from these mice showed no fluorescence.Transcription factors were introduced into human ES cells by the lipofection method. Expression of pancreatic endocrine hormone such as insulin was confirmed as early as two weeks after induction of differentiation. A method to induce cell differentiation from human ES cells to pancreatic endocrine cells was established.

Research Products

• [Journal Article] Efficient differentiation of human pluripotent stem cells into skeletal muscle cells by combining RNA-based MYOD1-expression and POU5F1-silencing. (2018)
  • Author(s): Akiyama T, Sato S, Chikazawa-Nohtomi N, Soma A, Kimura H, Wakabayashi S, Ko SBH, Ko MSH.
  • Journal Title: Sci Rep. Volume: 8 Issue: 1 Pages: 1189-1189
  • DOI: 10.1038/s41598-017-19114-y
  • Peer Reviewed / Open Access
• [Journal Article] Expression analysis of the endogenous Zscan4 locus and its coding proteins in mouse ES cells and preimplantation embryos (2017)
  • Author(s): Ishiguro K., Nakatake Y., Chikazawa-Nohtomi N., Kimura H., Akiyama T., Oda M., Ko SBH., Ko MSH.
  • Journal Title: In Vitro Cell.Dev.Biol.-Anim. Volume: 53 Issue: 2 Pages: 179-190
  • DOI: 10.1007/s11626-016-0097-y
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Zscan4 is expressed specifically during late meiotic prophase in both spermatogenesis and oogenesis (2017)
  • Author(s): Ishiguro K., Monti M., Akiyama T., Kimura H., Chikazawa-Nohtomi N., Sakota M., Sato S., Redi CA., Ko SBH., Ko MSH.
  • Journal Title: In Vitro Cell.Dev.Biol.-Anim. Volume: 53 Issue: 2 Pages: 167-178
  • DOI: 10.1007/s11626-016-0096-z
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors. (2017)
  • Author(s): Goparaju SK, Kohda K, Ibata K, Soma A, Nakatake Y, Akiyama T, Wakabayashi S, Matsushita M, Sakota M, Kimura H, Yuzaki M, Ko SB, Ko MS.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 42367-42367
  • DOI: 10.1038/srep42367
  • Peer Reviewed / Open Access
• [Journal Article] SCODE: An efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation (2017)
  • Author(s): Matsumoto, H., Kiryu, H., Furusawa, C., Ko, S.H., M., Ko, B.H., S., Gouda, N., Hayashi, T., Nikaido, I.
  • Journal Title: Bioinformatics Volume: 印刷中 Issue: 15 Pages: 2314-2321
  • DOI: 10.1093/bioinformatics/btx194
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Salt suppresses IFNγ inducible chemokines through the IFNγ-JAK1-STAT1 signaling pathway in proximal tubular cells. (2017)
  • Author(s): Arai Y, Takahashi D, Asano K, Tanaka M, Oda M, Ko SBH, Ko MSH, Mandai S, Nomura N, Rai T, Uchida S, Sohara E.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 46580-46580
  • DOI: 10.1038/srep46580
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epigenetic manipulation facilitates the generation of skeletal muscle cells from pluripotent stem cells. (2017)
  • Author(s): Tomohiko Akiyama, Shunichi Wakabayashi, Atsumi Soma, Saeko Sato, Yuhki Nakatake, Mayumi Oda, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B. H. Ko, Minoru S. H. Ko
  • Journal Title: Stem Cell International. Volume: 2017 Pages: 7215010-7215010
  • DOI: 10.1155/2017/7215010
  • Peer Reviewed / Open Access
• [Journal Article] Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors (2017)
  • Author(s): Matsushita Misako、Nakatake Yuhki、Arai Itaru、Ibata Keiji、Kohda Kazuhisa、Goparaju Sravan K.、Murakami Miyako、Sakota Miki、Chikazawa-Nohtomi Nana、Ko Shigeru B.H.、Kanai Takanori、Yuzaki Michisuke、Ko Minoru S.H.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 490 Issue: 2 Pages: 296-301
  • DOI: 10.1016/j.bbrc.2017.06.039
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification of transcription factors that promote the differentiation of human pluripotent stem cells into lacrimal gland epithelium-like cells. (2017)
  • Author(s): Hirayama M, Ko SBH, Kawakita T, Akiyama T, Goparaju SK, Soma A, Nakatake Y, Sakota M, Chikazawa-Nohtomi N, Shimmura S, Tsubota K, Ko MSH.
  • Journal Title: NPJ Aging Mech Dis Volume: 3 Issue: 1 Pages: 1-1
  • DOI: 10.1038/s41514-016-0001-8
  • Peer Reviewed / Open Access