Division of Pediatric General and Thoracic Surgery, Department of Surgery, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA.
Department of Oral Biology, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA.
Diabetes. 2021 Jul;70(7):1508-1518. doi: 10.2337/db20-1059. Epub 2021 Apr 27.
In contrast to the skin and the gut, where somatic stem cells and their niche are well characterized, a definitive pancreatic multipotent cell population in the adult pancreas has yet to be revealed. Of particular interest is whether such cells may be endogenous in patients with diabetes, and if so, can they be used for therapeutic purposes? In the current study, we used two separate reporter lines to target Cre-recombinase expression to the Lgr5- or glucagon-expressing cells in the pancreas. We provide evidence for the existence of a population of cells within and in the proximity of the ducts that transiently express the stem-cell marker Lgr5 during late gestational stages. Careful timing of tamoxifen treatment in ;R26 mice allowed us to show that these -expressing progenitor cells can differentiate into α-cells during pregnancy. Furthermore, we report on a spontaneous lineage conversion of α- to β-cells specifically after parturition. The contribution of Lgr5 progeny to the β-cell compartment through an α-cell intermediate phase early after pregnancy appears to be part of a novel mechanism that would counterbalance against excessive β-cell mass reduction during β-cell involution.
与皮肤和肠道不同，在那里已经很好地描述了体干细胞及其生态位，成人胰腺中的明确多能胰腺细胞群尚未被揭示。特别感兴趣的是这些细胞是否可能是糖尿病患者的内源性细胞，如果是这样，它们是否可以用于治疗目的？在本研究中，我们使用两种分离的报告基因系将 Cre 重组酶表达靶向到胰腺中 Lgr5 或胰高血糖素表达细胞。我们提供了证据证明在导管内和导管附近存在一群细胞，这些细胞在晚期妊娠阶段短暂表达干细胞标志物 Lgr5。在 ;R26 小鼠中谨慎地定时给予他莫昔芬治疗，使我们能够证明这些表达 - 的祖细胞可以在怀孕期间分化为α细胞。此外，我们报告了产后特有的自发的α细胞到β细胞的谱系转换。Lgr5 后代通过妊娠早期的α细胞中间阶段对β细胞区室的贡献似乎是一种新的机制的一部分，该机制可以抵消β细胞衰老期间β细胞质量的过度减少。
