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Single cell transcriptome profiling of mouse pancreatic β-lineage cells and hESC-derived β-like cells

ABSTRACT: While pancreatic β cells have been shown to originate from endocrine progenitors in ductal regions, it remains unclear precisely where β cells emerge and which transcripts define newborn β cells. Here, we used a mouse model “Ins1-GFP;Timer” that provides spatial information during β-cell neogenesis with high temporal resolution. Fluorescent imaging demonstrated that, as expected, some newborn β cells arise close to the ducts; unexpectedly, all the others arise away from the ducts and adjacent to blood vessels. Single-cell RNA-sequencing (scRNA-seq) demonstrated five distinct populations of newborn β cells, confirming the spatial heterogeneity of β-cell neogenesis, and integration analysis with scRNA-seq of hESC-derived β-like cells uncovered transcriptional similarity with the data in mouse β cells. Thus, the combination of time-resolved histological imaging with single-cell transcriptional mapping demonstrated novel features of spatial and transcriptional heterogeneity in β-cell neogenesis, which will lead to a better understanding of β-cell differentiation for future cell therapy.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE155742 | GEO | 2022/03/04

REPOSITORIES: GEO

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