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

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

Cell

Hubrecht Institute, Oncode Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), 3584 CT Utrecht, the Netherlands; University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands; Princess Maxima Centre for Pediatric Oncology, 3584 CS Utrecht, the Netherlands; Institute of Human Biology (IHB), Roche Pharma Research and Early Development, Roche innovation Centre, 4070 Basel, Switzerland. Electronic address:

Published: December 2024

AI Article Synopsis

  • The mammalian pancreas has three key parts: exocrine acini and ducts, along with endocrine islets, all originating from a common progenitor during development.
  • Researchers created 18 human fetal pancreas organoid lines from samples between 8-17 weeks of gestation, with four lines showing the ability to produce all three cell types while thriving in culture for over two years.
  • Single-cell RNA sequencing revealed LGR5 cells as crucial developmental stem cells, indicating that these organoids are capable of long-term growth and can differentiate into acinar, ductal, and endocrine cells.

Article 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 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.

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Source
http://dx.doi.org/10.1016/j.cell.2024.10.044DOI Listing

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