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Exploring the heterogeneity of endocrine progenitors in stem cell-islet differentiation

Exploring the heterogeneity of endocrine progenitors in stem cell-islet differentiation

Stem cell-derived islets normalize endogenous insulin production in people with type 1 diabetes. Our group is developing a differentiation protocol to produce pancreatic islets from induced pluripotent stem cells (iPSCs) for therapeutic use. One of the main problems plaguing islet differentiation from iPSCs is the production of off-target cells, such as immature ductal cells, mesenchymal-like cells, and intestinal enterochromaffin-like cells. Studies on fetal pancreas, however, identified the presence of enterochromaffin-like cells in developing pancreas. This may suggest enterochromaffin-like cells to be intermediary cells that can differentiate further into mature beta cells. Using scRNAseq, we confirmed the presence of enterochromaffin-like cells in stem cell islets generated from our and previously published protocols. Cell mapping of stem cell derived islets showed similarities between stem cell-derived enterochromaffin-like cells with fetal late endocrine progenitor cells. Trajectory analysis showed differentiation of endocrine progenitors into enterochromaffin-like cells before becoming mature endocrine cells. In vitro validations are needed to determine whether enterochromaffin-like cells could mature into functional pancreatic endocrine cells.