Department of Surgery, University of Pittsburgh Medical Center, One Children's Drive, 4401 Penn Avenue, Rangos Research Center, Pittsburgh, PA, 15244, USA.
Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, One Children's Drive, 4401 Penn Avenue, Rangos Research Center, Pittsburgh, PA, 15244, USA.
Sci Rep. 2017 Dec 13;7(1):17539. doi: 10.1038/s41598-017-17884-z.
Multipotent epithelial cells with high Aldehyde dehydrogenase activity have been previously reported to exist in the adult pancreas. However, whether they represent true progenitor cells remains controversial. In this study, we isolated and characterized cells with ALDH activity in the adult mouse or human pancreas during physiological conditions or injury. We found that cells with ALDH activity are abundant in the mouse pancreas during early postnatal growth, pregnancy, and in mouse models of pancreatitis and type 1 diabetes (T1D). Importantly, a similar population of cells is found abundantly in healthy children, or in patients with pancreatitis or T1D. We further demonstrate that cells with ALDH activity can commit to either endocrine or acinar lineages, and can be divided into four sub-populations based on CD90 and Ecadherin expression. Finally, our in vitro and in vivo studies show that the progeny of ALDH1/CD90/Ecad cells residing in the adult mouse pancreas have the ability to initiate Pancreatic and duodenal homeobox (Pdx1) expression for the first time. In summary, we provide evidence for the existence of a sortable population of multipotent non-epithelial cells in the adult pancreas that can commit to the pancreatic lineage following proliferation and mesenchymal to epithelial transition (MET).
先前有报道称，成年胰腺中存在具有高醛脱氢酶活性的多能上皮细胞。然而，它们是否代表真正的祖细胞仍存在争议。在这项研究中，我们在生理条件或损伤下从成年小鼠或人胰腺中分离和鉴定了具有 ALDH 活性的细胞。我们发现，在小鼠出生后早期生长、妊娠以及胰腺炎和 1 型糖尿病（T1D）的小鼠模型中，具有 ALDH 活性的细胞在小鼠胰腺中大量存在。重要的是，在健康儿童或胰腺炎或 T1D 患者中也发现了大量类似的细胞。我们进一步证明，具有 ALDH 活性的细胞可以向内分泌或腺泡谱系分化，并可以根据 CD90 和 Ecadherin 的表达分为四个亚群。最后，我们的体外和体内研究表明，成年小鼠胰腺中 ALDH1/CD90/Ecad 细胞的后代首次具有启动胰腺十二指肠同源盒 1（Pdx1）表达的能力。总之，我们提供了证据证明成年胰腺中存在可分选的多能非上皮细胞群，这些细胞在增殖和间充质到上皮转化（MET）后可向胰腺谱系分化。
