Pancreatic cell fate specification - insights into developmental mechanisms and their application for lineage reprogramming

Sep 29, 2026

Uploaded by dabgoudw

Diabetes arises from insufficient functional pancreatic β-cell mass, driven by autoimmune destruction of insulin-producing β-cells or by cell death and de-differentiation under insulin resistance. Reprogramming cell types located close in developmental lineage to β-cells offers a route to replenish β-cell mass and potentially treat diabetes. This review surveys recent progress in pancreas development and lineage reprogramming, examines how reprogrammed cells can reveal developmental roadblocks to identity change, and outlines key challenges for advancing lineage reprogramming toward pancreatic cell generation.

LanguageEnglish

CategoryHealthcare

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Pages14

Reading Time35 min

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Introduction

Pancreas development and β-cell dysfunction

Expanding the pancreatic transcriptional network

Europe PMC unders uthManuscripts Europe M eC und Author Manuscripts | Europe PMC Funders Group
Author Manuscript
Curr Opin Genet Dev. Author manuscript; available in PMC 2026 January 06. | | --- | | Published in final edited form as:
Curr Opin Genet Dev. 2021 October 01; 70: 32–39. doi:10.1016/j.gde.2021.05.003 .
Pancreatic cell fate specification: insights into developmental mechanisms and their application for lineage reprogramming
Abigail Isaacson, Francesca M Spagnoli
Centre for Stem Cells and Regenerative Medicine, King’s College London, Guy’s Hospital, Floor 28, Tower Wing, Great Maze Pond,, London SE1 9RT, UK.
Abstract
Diabetes is a group of metabolic disorders, which results from insufficient functional pancreatic β-cell mass either due to the autoimmune destruction of insulin producing β-cells, or their death or de-differentiation as compensation for insulin resistance. The ability to reprogram cell types within close developmental proximity to β-cells offers a strategy to replenish β-cell mass and a future possible treatment of diabetes. Here, we review recent advances in the fields of pancreas development and lineage reprogramming. We also probe the possibility of using reprogrammed cells as an approach by which to further understand developmental mechanisms, in particular roadblocks to changing cell identity. Finally, we highlight fundamental challenges that need to be overcome to advance lineage reprogramming for generating pancreatic cells.
Introduction
The pancreas is an endoderm-derived compound gland composed of multiple cell types that serve either its endocrine or exocrine functions [1] . In the exocrine pancreas, acini cluster around the terminus of each duct, which forms a tubular network that facilitates the transport of enzymes and zymogens synthesised by acinar cells (Figure 1) . The endocrine pancreas, which represents the minority (1–2%) of the organ volume, consists of five hormone-producing cell types that are localised within the islets of Langerhans. The most abundant islet cell type is the insulin-secreting β-cell; these cells are responsible for maintaining glucose homeostasis by sensing blood glucose levels and secreting insulin accordingly into the islet vasculature [2]. Loss or dysfunction of β-cells results in diabetes, the most common pancreas-related disorder [3,4] .
This work is licensed under a BY 4.0 International license.
Correspondence to: Francesca M Spagnoli.
Corresponding author: Spagnoli, Francesca M ([francesca.spagnoli@kcl.ac.uk](francesca.spagnoli@kcl.ac.uk)).
Edited by Stefan H Stricker, Benedikt Berninger and Magdalena Götz For a complete overview see the Issue and the Editorial
This review comes from a themed issue on Cell reprogramming, regeneration and repair Conflict of interest statement
Nothing declared.
CRediT authorship contribution statement
Abigail Isaacson: Conceptualization, Writing-original draft. Francesca M Spagnoli: Conceptualization, Writing-review & editing. | Europe PMC unders uthManuscripts Europe M eC und Author Manuscripts Isaacson and Spagnoli Page 2 All pancreatic cell types arise from a common progenitor population that becomes specified as the result of temporal and spatial integration of extrinsic signals from the surrounding microenvironment and intrinsic genetic determinants. Numerous excellent reviews have been written on pancreatic development both in the mouse and human [1,2,5–7] and should be consulted for a more comprehensive view. Here, we summarize the main events of this multi-step process in Figure 1. Despite the mapping of well-defined transcriptional networks and signaling pathways at key developmental junctions, our understanding of pancreatic cell fate specification is still ever-increasing; this is largely due to improvements in genetic cell isolation strategies used in combination with multi-omics tools that have enabled the identification of new genetic factors as well

FAQs

What causes diabetes in this review’s framework?

Diabetes is linked to insufficient functional pancreatic β-cell mass due to autoimmune destruction, or because β-cells undergo death or de-differentiation to compensate for insulin resistance.

Why is lineage reprogramming considered a potential strategy for diabetes treatment?

Reprogramming cell types that are developmentally close to β-cells could replenish β-cell mass, offering a future possible therapeutic approach.

How can reprogrammed cells help researchers understand developmental mechanisms?

By testing identity changes, researchers can probe developmental mechanisms, especially barriers that prevent changing cell identity during reprogramming.

Sep 29, 2026

Uploaded by dabgoudw