TY - JOUR
T1 - Long-term in vitro expansion of a human fetal pancreas stem cell that generates all three pancreatic cell lineages
AU - Andersson-Rolf, Amanda
AU - Groot, Kelvin
AU - Korving, Jeroen
AU - Begthel, Harry
AU - Hanegraaf, Maaike A J
AU - VanInsberghe, Michael
AU - Salmén, Fredrik
AU - van den Brink, Stieneke
AU - Lopez-Iglesias, Carmen
AU - Peters, Peter J
AU - Krueger, Daniel
AU - Beumer, Joep
AU - Geurts, Maarten H
AU - Alemany, Anna
AU - Gehart, Helmuth
AU - Carlotti, Françoise
AU - de Koning, Eelco J P
AU - Chuva de Sousa Lopes, Susana M
AU - van Oudenaarden, Alexander
AU - van Es, Johan H
AU - Clevers, Hans
N1 - Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
PY - 2024/12/26
Y1 - 2024/12/26
N2 - 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.
AB - 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.
KW - Humans
KW - Cell Lineage
KW - Pancreas/cytology
KW - Organoids/cytology
KW - Fetus/cytology
KW - Cell Differentiation
KW - Receptors, G-Protein-Coupled/metabolism
KW - Fetal Stem Cells/cytology
KW - Cell Proliferation
KW - Single-Cell Analysis
KW - Islets of Langerhans/cytology
KW - Mice
KW - Animals
KW - Acinar Cells/cytology
U2 - 10.1016/j.cell.2024.10.044
DO - 10.1016/j.cell.2024.10.044
M3 - Article
C2 - 39626658
SN - 0092-8674
VL - 187
SP - 7394-7413.e22
JO - Cell
JF - Cell
IS - 26
ER -