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Review
, 22 (4), 255-64

Pancreatic Islet Cell Development and Regeneration

Affiliations
Review

Pancreatic Islet Cell Development and Regeneration

Anthony I Romer et al. Curr Opin Endocrinol Diabetes Obes.

Abstract

Purpose of review: This review will discuss recent advances in understanding mouse and human pancreatic islet cell development, novel concepts related to β cell dysfunction and improved approaches for replenishing β cells to treat diabetes.

Recent findings: Considerable knowledge about pancreatic islet development and function has been gained using model systems with subsequent validation in human tissues. Recently, several rodent studies have revealed that differentiated adult islet cells retain remarkable plasticity and can be converted to other islet cell types by perturbing their transcription factor profiles. Furthermore, significant advances have been made in the generation of β-like cells from stem cell populations. Therefore, the generation of functionally mature β cells by the in-situ conversion of non-β cell populations or by the directed differentiation of human pluripotent stem cells could represent novel mechanisms for replenishing β cells in diabetic patients.

Summary: The overall conservation between mouse and human pancreatic development, islet physiology and etiology of diabetes encourages the translation of novel β cell replacement therapies to humans. Further deciphering the molecular mechanisms that direct islet cell regeneration, plasticity and function could improve and expand the β cell replacement strategies for treating diabetes.

Conflict of interest statement

None of the authors declare a conflict of interest.

Figures

Figure 1
Figure 1. Transcription Factors direct pancreatic islet cell development
Pancreatic bud development from foregut endoderm depends on the TFs Pdx1, Ptf1a, Mnx1, Foxa1, Foxa2, Gata4 and Gata6. Human pancreas specification has greater dependency on GATA6 possibly due to a lack of GATA4 expression in the foregut endoderm prior to pancreas specification. Lineage restriction of multi-potent pancreatic progenitor populations towards exocrine progenitor cells and ductal/endocrine bi-potent progenitor cells occurs during their segregation to the tips and trunks of the developing pancreatic arboretum respectively and is directed by mutual repression between Nkx6.1 and Ptf1a. Neurog3 is essential for the differentiation of trunk progenitors to hormone producing islet cells in mice but not humans; suggesting functional redundancy by other factors. Specific combinations of functionally conserved TFs are required for Neurog3+ precursors to differentiate into specialized mono-hormonal islet endocrine cells. In humans NKX2-2 is not expressed until endocrine cell differentiation, which may explain why many of the early endocrine cells are poly-hormonal. TFs that differ in human versus mouse by their expression pattern or genetic functions are highlighted in grey with a superscript H to delineate “human”.

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