Pancreatic Plasticity and Beta Cell Maturation
By: Mari Yamamoto
In 2013, researchers from the University of Pennsylvania published a paper on the epigenomic plasticity of pancreatic cells. Transcriptome analysis revealed a more plastic epigenomic state for alpha cells compared to beta and exocrine cells. They were also able to promote alpha to beta cell programming by manipulating the histone methylation signature of the cells, suggesting that this sort of manipulation could be important in cell reprogramming.
In the past few years, further research relating to this plasticity of pancreatic cells has been done. Read on to find out more.
A Neogenic Niche
This 2018 study describes a “virgin” population of beta cells in mice, in the intermediate stage between alpha and beta cell transdifferentiation. These form at a “neogenic niche” at the islet periphery and express insulin while lacking other markers like urocortin 3. This microenvironment at the islet periphery supports lifelong conversion between alpha and beta cells. The plasticity described regarding beta cell identity could have future potential in aiding beta cell regeneration.
Urocortin 3 (Ucn3) is a peptide hormone marker that is closely associated with beta cell maturity, but whether it’s necessary for said maturation was still unestablished. A very recent paper published in July 2020 explored this with the genetic deletion of Ucn3 in mice. The researchers found that the Ucn3-negative mice did not cause a loss of beta cell maturity or an increase in dedifferentiation. In addition, the virgin beta cells (described in the previous paper) were still present at the islet periphery. According to these results, Ucn3 is not necessary for beta cell maturation despite being a marker for it.
The Last Word: These findings have the potential to spur future research with cell reprogramming, as well as with beta cell regeneration. For example, studies with beta cell markers (such as Ucn3) could pave the way for generating beta cells from stem cells.
- Bramswig NC, Everett LJ, Schug J, et al. Epigenomic plasticity enables human pancreatic α to β cell reprogramming. J Clin Invest. 2013;123(3):1275-1284. doi:10.1172/JCI66514
- van der Meulen T, Mawla AM, DiGruccio MR, et al. Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets. Cell Metab. 2017;25(4):911-926.e6. doi:10.1016/j.cmet.2017.03.017
- Huang JL, Lee S, Hoek P, van der Meulen T, Van R, Huising MO. Genetic deletion of Urocortin 3 does not prevent functional maturation of beta cells. J Endocrinol. 2020;246(1):69-78. doi:10.1530/JOE-19-0535