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

Autor:	Andersson-Rolf A; 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. Electronic address: a.andersson@hubrecht.eu., Groot K; 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., Korving J; 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., Begthel H; 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., Hanegraaf MAJ; Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., VanInsberghe M; 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., Salmén F; 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., van den Brink S; 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., Lopez-Iglesias C; The Maastricht Multimodal Molecular Imaging Institute, 6229 ER Maastricht, the Netherlands., Peters PJ; The Maastricht Multimodal Molecular Imaging Institute, 6229 ER Maastricht, the Netherlands., Krueger D; 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., Beumer J; Institute of Human Biology (IHB), Roche Pharma Research and Early Development, Roche innovation Centre, 4070 Basel, Switzerland., Geurts MH; 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., Alemany A; Department of Anatomy and Embryology, Leiden University Medical Centre, 2333 ZA Leiden, the Netherlands., Gehart H; ETH Zurich, Institute of Molecular Health Sciences, 8093 Zürich, Schweiz., Carlotti F; Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., de Koning EJP; Department of Internal Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Chuva de Sousa Lopes SM; Department of Anatomy and Embryology, Leiden University Medical Centre, 2333 ZA Leiden, the Netherlands., van Oudenaarden A; 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., van Es JH; 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., Clevers H; 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: h.clevers@hubrecht.eu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Dec 26; Vol. 187 (26), pp. 7394-7413.e22. Date of Electronic Publication: 2024 Dec 02.
DOI:	10.1016/j.cell.2024.10.044
Abstrakt:	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. Competing Interests: Declaration of interests H.C. is an inventor on patents held by the Royal Netherlands Academy of Arts and Sciences that cover organoid technology and a co-founder of Xilis, Duke University (NC). He is currently Head of pharma Research and Early Development (pRED) at Roche, Basel, Switzerland. H.C.’s full disclosure is given at https://www.uu.nl/staff/JCClevers/. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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