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题目:
Small molecules facilitate the reprogramming of mouse fibroblasts into pancreatic lineages.
作者:
Li(Ke),Zhu(Saiyong),Russ(Holger A),Xu(Shaohua),Xu(Tao),Zhang(Yu),Ma(Tianhua),Hebrok(Matthias),Ding(Sheng)
状态:
发布时间2014-02-10 , 更新时间 2016-10-25
期刊:
Cell Stem Cell
摘要:
Pancreatic β cells are of great interest for the treatment of type 1 diabetes. A number of strategies already exist for the generation of β cells, but a general approach for reprogramming nonendodermal cells into β cells could provide an attractive alternative in a variety of contexts. Here, we describe a stepwise method in which pluripotency reprogramming factors were transiently expressed in fibroblasts in conjunction with a unique combination of soluble molecules to generate definitive endoderm-like cells that did not pass through a pluripotent state. These endoderm-like cells were then directed toward pancreatic lineages using further combinations of small molecules in vitro. The resulting pancreatic progenitor-like cells could mature into cells of all three pancreatic lineages in vivo, including functional, insulin-secreting β-like cells that help to ameliorate hyperglycemia. Our findings may therefore provide a useful approach for generating large numbers of functional β cells for disease modeling and, ultimately, cell-based therapy.
语言:
eng
DOI:

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