Author response: In vivo reprogramming of pancreatic acinar cells to three islet endocrine subtypes
Year: 2014
Type: peer-review
Abstract: In mammals, the pancreas is responsible for controlling blood sugar by secreting insulin from specialized β-cells. Other cells in the pancreas, called δ-cells and α-cells, secrete other hormones to assist the β-cells. Diabetes is caused when this system breaks down: either the body attacks its own β-cells (type I diabetes), or the body stops responding properly to insulin (type II). Type I diabetes is usually treated with insulin injections, but there is increasing interest in the possibility of replacing the defective β-cells instead. Building on previous work in which a fourth type of pancreatic cell, called an acinar cell, was reprogrammed to become a β-cell, Li et al. have now shown that the same technique can be used to produce α- and δ-cells as well. Just as the reprogrammed β-cells secreted insulin, like real β-cells, the reprogrammed α- and δ-cells also behaved like real α- and δ-cells. The reprogramming technique relies on using a combination of three transcription factors—which are called Ngn3, Pdx1 and Mafa—to treat the acinar cells from mice. Previously, it was shown that using a combination of all three transcription factors reprogrammed the acinar cells to become β-cells. Now, Li et al. show that the Ngn3 transcription factor on its own appears to suppress certain genes that are usually expressed in acinar cells, and goes on to cause the acinar cells to become δ-cells. However, a combination of Ngn3 and Mafa produces a mixture of α- and δ-cells. The next challenge is to adapt this reprogramming technique to generate different types of hormone secreting cells from human tissue sources in order to explore its therapeutic potential.
Institutions: Harvard University, McMaster University, Vanderbilt University
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W2989194337