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Updated: Mar 8, 2026

Differentiation of Human Pluripotent Stem Cells into Insulin-Producing Islet Clusters
Published on: June 23, 2023
Differentiation of Islet Progenitors Regulated by Nicotinamide into Transcriptome-Verified β Cells That Ameliorate
Fang-Xu Jiang1,2, Kevin Li1,2, Michael Archer3
1Islet Cell Development Program, Harry Perkins Institute of Medical Research, and Centre for Medical Research.
Abstract:
Developmental stage-specific differentiation of stem or progenitor cells into safe and functional cells is of fundamental importance in regenerative medicine, including β-cell replacement. However, the differentiation of islet progenitor cells (IPCs) into insulin-secreting β cells remains elusive. Here, we report that the multifunctional molecule nicotinamide (NIC) is a specific differentiation regulator of mouse IPCs. The differentiated cells regulated by NIC exhibited many characteristics of adult β cells, including ameliorating preclinical diabetes and a highly comparable transcriptome profile. Gene set enrichment analysis showed that during differentiation, numerous IPC transcription factor genes, including Ngn3, Pax4, Fev, and Mycl1, were all down regulated. Pharmacological, biochemical, and gene knockdown analyses collectively demonstrated that NIC regulated the differentiation via inhibiting Sirt1 (silent information regulator transcript 1). Finally, NIC also regulates human IPC differentiation. Thus, our study advances islet developmental biology and impacts on translational research and regenerative therapies to diabetes and other diseases. Stem Cells 2017;35:1341-1354.
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