Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston 02114, USA.
Stem Cell Reports. 2018 Mar 13;10(3):725-738. doi: 10.1016/j.stemcr.2018.01.028. Epub 2018 Mar 1.
Pancreatic duct epithelial cells have been suggested as a source of progenitors for pancreatic growth and regeneration. However, genetic lineage-tracing experiments with pancreatic duct-specific Cre expression have given conflicting results. Using immunofluorescence and flow cytometry, we show heterogeneous expression of both HNF1β and SOX9 in adult human and murine ductal epithelium. Their expression was dynamic and diminished significantly after induced replication. Purified pancreatic duct cells formed organoid structures in 3D culture, and heterogeneity of expression of Hnf1β and Sox9 was maintained even after passaging. Using antibodies against a second cell surface molecule CD51 (human) or CD24 (mouse), we could isolate living subpopulations of duct cells enriched for high or low expression of HNF1β and SOX9. Only the CD24 (Hnfβ/Sox9) subpopulation was able to form organoids.
胰腺导管上皮细胞被认为是胰腺生长和再生的祖细胞来源。然而,具有胰腺导管特异性 Cre 表达的遗传谱系追踪实验给出了相互矛盾的结果。通过免疫荧光和流式细胞术,我们显示成年人和鼠类导管上皮中 HNF1β 和 SOX9 的表达存在异质性。它们的表达是动态的,并在诱导复制后显著减少。纯化的胰腺导管细胞在 3D 培养中形成类器官结构,即使传代后,Hnf1β 和 Sox9 的表达异质性也得以维持。使用针对第二个细胞表面分子 CD51(人)或 CD24(鼠)的抗体,我们可以分离出高或低表达 HNF1β 和 SOX9 的导管细胞的活亚群。只有 CD24(Hnfβ/Sox9)亚群能够形成类器官。