[522] Mechanisms involved in specifying and determining the different pancreatic cell types: cell plasticity and regeneration by cell type interconversion
Prof. Herrera's group studies the genetic regulation of pancreas development and, more extensively, of pancreas regeneration after injury. To address the biological questions related to the regeneration of insulin-producing beta-cells in diabetic situations, they use human pancreatic islets obtained from deceased donors. In parallel, they produce and use different lines of transgenic mice, which are powerful genetic tools to study the natural history of the human disease.
The regeneration potential of adult pancreata is studied with different approaches. New transgenic mice in which specific pancreatic cell types can be conditionally ablated and/or genetically tagged are used to analyze the process of reconstitution of new insulin-producing cells after they are lost, like in diabetes. The laboratory of Prof. Herrera explores the extent and mechanisms of regeneration of insulin-producing cells in the adult pancreas, at different ages.
Observations made in Prof. Herrera’s lab and reported in studies published in the journals Nature (2010, 2014 and 2019), Nature Cell Biology (2018) and Nature Communications (2021), have led to an innovative breakthrough in the approach to developing new cell replacement therapies for diabetes. Still an early discovery, Prof. Herrera’s team has shown that the adult pancreas retains the ability to generate new insulin-producing cells after the near total loss of functional beta-cells, which are the native insulin producers. This unexpected finding revealed a high degree of cell plasticity, for nearly all the reconstituted beta-like cells were indeed adult specialised mature endocrine non-beta cells (alpha-, delta-, and gamma-cells), which had spontaneously reprogrammed to produce insulin.
This functional interconversion of different cell types had never been described in mammals before.
Beyond diabetes, any degenerative disease, i.e. a condition resulting from massive and premature cell death, will likely benefit from this paradigm shift. This is particularly striking now, for Prof. Herrera’s laboratory has shown that the cellular plasticity is also a feature of human pancreatic islet non-beta cells.
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