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Generation of Human Islet Cell-Type-Specific Identity Genesets

ABSTRACT: Generation of mature cells with stable functional identities is crucial for developing cell-based replacement therapies. Current global efforts to produce insulin-secreting beta-like cells to treat diabetes are hampered by the lack of tools to reliably assess cellular identity. We conducted a thorough single-cell transcriptomics meta-analysis to generate robust genesets defining the identity of human adult alpha-, beta-, gamma- and delta-cells. After extensive validation, we showed the efficacy of the novel genesets to define changes in islet cell identity, whether during embryonic development or in different experimental setups aimed at developing new functional glucose-responsive insulin-secreting cells, such as through pluripotent stem-cell differentiation or islet cell reprogramming protocols. Finally, we evaluated whether the perturbed metabolic conditions typical of diabetes influence islet cell identity. We observed that alpha-cells from diabetic donors exhibit an altered phenotype. In conclusion, these novel genesets represent valuable tools that robustly benchmark gain and loss in islet cell identity traits.

ORGANISM(S): Homo sapiens

PROVIDER: GSE150724 | GEO | 2021/06/26

REPOSITORIES: GEO

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