Yamaguchi Junpei, Liss Andrew S, Sontheimer Alexandra, Mino-Kenudson Mari, Castillo Carlos Fernández-Del, Warshaw Andrew L, Thayer Sarah P
Andrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Andrew L. Warshaw Institute for Pancreatic Cancer Research, Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
Stem Cell Res. 2015 Jul;15(1):190-202. doi: 10.1016/j.scr.2015.05.006. Epub 2015 May 19.
Pancreatic duct glands (PDGs) have molecular features known to mark stem cell niches, but their function remains to be determined. To investigate the role of PDGs as a progenitor niche, PDGs were analyzed in both humans and mice. Cells were characterized by immunohistochemistry and microarray analysis. In vivo proliferative activity and migration of PDG cells were evaluated using a BrdU tag-and-chase strategy in a mouse model of pancreatitis. In vitro migration assays were used to determine the role of trefoil factor (TFF) -1 and 2 in cell migration. Proliferative activity in the pancreatic epithelium in response to inflammatory injury is identified principally within the PDG compartment. These proliferating cells then migrate out of the PDG compartment to populate the pancreatic duct. Most of the pancreatic epithelial migration occurs within 5days and relies, in part, on TFF-1 and -2. After migration, PDG cells lose their PDG-specific markers and gain a more mature pancreatic ductal phenotype. Expression analysis of the PDG epithelium reveals enrichment of embryonic and stem cell pathways. These results suggest that PDGs are an epithelial progenitor compartment that gives rise to mature differentiated progeny that migrate to the pancreatic duct. Thus PDGs are a progenitor niche important for pancreatic epithelial regeneration.
胰腺导管腺（PDGs）具有已知可标记干细胞龛的分子特征，但其功能仍有待确定。为了研究PDGs作为祖细胞龛的作用，对人类和小鼠的PDGs进行了分析。通过免疫组织化学和微阵列分析对细胞进行表征。在胰腺炎小鼠模型中，使用BrdU标记追踪策略评估PDG细胞的体内增殖活性和迁移。体外迁移试验用于确定三叶因子（TFF）-1和-2在细胞迁移中的作用。炎症损伤后胰腺上皮中的增殖活性主要在PDG区域内被识别。这些增殖细胞随后从PDG区域迁移出来以填充胰腺导管。大多数胰腺上皮迁移发生在5天内，部分依赖于TFF-1和-2。迁移后，PDG细胞失去其PDG特异性标记并获得更成熟的胰腺导管表型。PDG上皮的表达分析显示胚胎和干细胞途径的富集。这些结果表明，PDGs是一个上皮祖细胞区域，可产生迁移到胰腺导管的成熟分化后代。因此，PDGs是胰腺上皮再生的重要祖细胞龛。
