University of California, San Diego (UCSD)

Regulation of Pancreas Differentiation by Long Noncoding RNAs

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In patients suffering from diabetes, insulin-producing β-cells are lost or become defective, resulting in dependence on daily insulin injections. Transplantation of donor β-cells can restore the body’s ability to regulate blood sugar levels and improve the quality of life for diabetics. However, the limited number of human donors restricts the applicability of this therapy. Methods for producing replacement β-cells for transplantation are highly sought after. One promising strategy is to coax other human body cells into becoming β-cells by adding or removing specific factors, a process called “reprogramming”. While there has been some success in reprogramming related cell-types into insulin-producing cells, the conversion is inefficient and slow. This is likely because important factors that may facilitate the conversion process are missing. We hypothesize that “long noncoding RNAs” (lncRNAs) may be the missing factor that could facilitate reprogramming of cells toward a B-cell fate. lncRNAs are non-coding RNAs that are important regulators of cell fate commitment. We have identified a group of lncRNAs that are produced in the developing pancreas at precisely coordinated time points, suggesting that they play important roles in pancreas specification and development. I propose to determine the function of these lncRNAs in pancreas development by depleting or mis-expressing these lncRNAs in embryonic stem cells and determine whether and how these manipulations affect the ability of these cells to develop into pancreas or adopt alternative organ cell fates. Results from our study could have important implications in devising reprogramming strategies to generate β-cells from other organ cell types.