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Dryad

Bulk and single-cell RNA-seq of human fetal pancreatic organoids

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Dec 07, 2024 version files 449.27 MB

Abstract

The mammalian pancreas consists of three epithelial compartments: the acini and ducts of the exocrine pancreas and the endocrine islets of Langerhans. Murine studies indicate that these three compartments derive from a transient, common pancreatic progenitor. Here, we report the derivation of 18 human fetal pancreas organoid (hfPO) lines from gestational week 8-17 (8-17GW) fetal pancreas samples. Four of these lines, derived from 15-16GW samples, generate acinar-, ductal- and endocrine lineage cells while expanding exponentially for >2 years under optimized culture conditions. Single-cell RNA sequencing identifies rare LGR5+ cells in the fetal pancreas and hfPOs as the root of the developmental hierarchy. These LGR5+ cells share multiple markers with adult gastrointestinal tract stem cells. Organoids derived from single LGR5+ organoid-derived cells recapitulate this tri-potency in vitro. We describe a human fetal tri-potent stem/progenitor cell, capable of long-term expansion in vitro and of generating all three pancreatic cell lineages.