University of Dundee

'Chemical and metabolic control of pluripotent stem cell differentiation into pancreatic β cells'

Event Date: 
Friday, September 29, 2017 - 11:00
Event Location: 
CTIR Sir Kenneth and Lady Noreen Murray Seminar Room
Professor Tomo Tanaka FRSE
Professor Victoria Cowling
Event Speaker: 
Prof Shoen Kume
Tokyo Institute of Technology, School of Life Science and Technology
Event Type: 


ES cells and iPS cells are considered to be potential alternative cell sources for the transplantation therapy as well as cell models for biological studies. Up to date, studies to generate the pancreatic beta cells from pluripotent stem cells have achieved remarkable progresses. However, it still remain elusive whether the derived pancreatic beta cells resemble the human beta cells and could be used in clinical settings. 
We have been trying to improve the efficiency of differentiation and the maturation of the derived insulin-producing beta cells from human ES/iPS cells, through screening for novel small molecular compounds that promote differentiation and/or proliferation of pancreatic beta-cells. We identified molecules that function in regulating pancreatic beta cell differentiation and dedifferentiation.
Besides chemical screening, we also analyzed the importance of amino acids in the media. We found that methionine metabolism is crucial for the maintenance of pluripotency in human pluripotent cells. Deprival of methionine rendered the cells at a poised state for differentiation, and thus increased the efficiency for differentiation. 
Sakano D., Choi S, Kataoka M, Shiraki N, Uesugi M, Kume K, Kume S. Dopamine D2 receptor-mediated regulation of beta cell mass. Stem Cell Report 7, 95-109, 2016.
Ogaki S*, Morooka M*, Otera K and Kume S. A cost effective system for differentiation of intestinal epithelium from human induced pluripotent stem cells. Sci Rep 5: 17297, 2015.
Shahjalal HM, Shiraki N, Sakano D, Kikawa H, Ogaki S, Baba H, Kume K., Kume S. Generation of insulin-producing beta-like cells from human iPS cells in a defined and completely Xeno-free culture system. J. Mol. Cell Biol. 6, 394-408, 2014.
Shiraki N., Shiraki Y., Tsuyama T., Obata F, Miura M, Nagae G, Aburatani H., Kume K, Endo F, Kume S*. Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells. Cell Metab. 19, 780-794, 2014.