近日，荷兰皇家艺术与科学院Hans Clevers等研究人员合作发现，人类胎儿胰腺干细胞的长期体外扩增能够生成三种胰腺细胞谱系。2024年12月2日，《细胞》杂志在线发表了这项成果。

研究人员报告了从妊娠8至17周（8-17 GW）的胎儿胰腺样本中衍生的18条人类胎儿胰腺类器官（hfPO）谱系。其中特别是来自15至16 GW样本的四条谱系，能够在优化培养条件下，持续扩增超过2年，并生成腺泡、导管和内分泌谱系的细胞。

单细胞RNA测序揭示了胎儿胰腺和hfPO中稀有的LGR5+细胞，它们是胰腺发育层级的根源。这些LGR5⁺细胞与成人胃肠道干细胞共享多个标记物。由单个LGR5⁺类器官来源细胞衍生的类器官能够在体外再现这种三能性。研究人员描述了一种能够长期体外扩增，并能生成三种胰腺细胞谱系的人类胎儿三能性干/祖细胞。

研究人员表示，哺乳动物胰腺由三个上皮区域组成：外分泌胰腺的腺泡和导管，以及内分泌的胰岛。小鼠研究表明，这三个区域来源于一个短暂的、共同的胰腺祖细胞。

附：英文原文

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

Author: 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, Franoise Carlotti, Eelco J.P. de Koning, Susana M. Chuva de Sousa Lopes, Alexander van Oudenaarden, Johan H. van Es, Hans Clevers

Issue&Volume: 2024-12-02

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.

DOI: 10.1016/j.cell.2024.10.044

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01254-6