Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages

Amanda Andersson-Rolf, Kelvin Groot, Jeroen Korving, Harry Begthel, Maaike A J Hanegraaf, Michael VanInsberghe, Fredrik Salmén, Stieneke van den Brink, Carmen Lopez-Iglesias, Peter J Peters, Daniel Krueger, Joep Beumer, Maarten H Geurts, Anna Alemany, Helmuth Gehart, Françoise Carlotti, Eelco J P de Koning, Susana M Chuva de Sousa Lopes, Alexander van Oudenaarden, Johan H van EsHans Clevers

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

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 derivation of 18 human fetal pancreas organoid (hfPO) lines from gestational weeks 8-17 (8-17 GWs) fetal pancreas samples. Four of these lines, derived from 15 to 16 GWs 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 fetal pancreas and in 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 tripotency in vitro. We describe a human fetal tripotent stem/progenitor cell capable of long-term expansion in vitro and of generating all three pancreatic cell lineages.

Originele taal-2Engels
Pagina's (van-tot)7394-7413.e22
TijdschriftCell
Volume187
Nummer van het tijdschrift26
DOI's
StatusGepubliceerd - 26 dec. 2024

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