[PDF][PDF] Reprogrammed stomach tissue as a renewable source of functional β cells for blood glucose regulation

C Ariyachet, A Tovaglieri, G Xiang, J Lu, MS Shah… - Cell stem cell, 2016 - cell.com
C Ariyachet, A Tovaglieri, G Xiang, J Lu, MS Shah, CA Richmond, C Verbeke, DA Melton…
Cell stem cell, 2016cell.com
The gastrointestinal (GI) epithelium is a highly regenerative tissue with the potential to
provide a renewable source of insulin+ cells after undergoing cellular reprogramming. Here,
we show that cells of the antral stomach have a previously unappreciated propensity for
conversion into functional insulin-secreting cells. Native antral endocrine cells share a
surprising degree of transcriptional similarity with pancreatic β cells, and expression of β cell
reprogramming factors in vivo converts antral cells efficiently into insulin+ cells with close …
Summary
The gastrointestinal (GI) epithelium is a highly regenerative tissue with the potential to provide a renewable source of insulin+ cells after undergoing cellular reprogramming. Here, we show that cells of the antral stomach have a previously unappreciated propensity for conversion into functional insulin-secreting cells. Native antral endocrine cells share a surprising degree of transcriptional similarity with pancreatic β cells, and expression of β cell reprogramming factors in vivo converts antral cells efficiently into insulin+ cells with close molecular and functional similarity to β cells. Induced GI insulin+ cells can suppress hyperglycemia in a diabetic mouse model for at least 6 months and regenerate rapidly after ablation. Reprogramming of antral stomach cells assembled into bioengineered mini-organs in vitro yielded transplantable units that also suppressed hyperglycemia in diabetic mice, highlighting the potential for development of engineered stomach tissues as a renewable source of functional β cells for glycemic control.
cell.com