Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration
Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration
复制标题
DOI：
10.1053/j.gastro.2004.12.008
复制
发表时间：
2005-03-01
期刊：
影响因子：
29.4
通讯作者：
Jensen, J
中科院分区：
文献类型：
--
作者：
Jensen, JN;Cameron, E;Jensen, J
背景和目标：哺乳动物的胰腺具有很强的再生潜力，但器官恢复的起源尚不清楚，也不知道这种过程在多大程度上反映了胰腺的发育。为了确定成年小鼠胰腺再生相关的细胞分化变化，我们比较了雨蛙素诱导胰腺炎后的再生与正常胰腺发育的再生。研究方法：通过对雨蛙素处理的和对照胰腺中的成人和胚胎胰腺标志物进行比较组织学，我们解决了细胞增殖和分化（淀粉酶、DBA-凝集素、胰岛素、胰高血糖素、β-连环蛋白、E-钙粘蛋白、Pdx 1、Nkx 6.1、Notch 1、Notch 2、Jagged 1、Jagged 2、Hes 1），从而描述了组织恢复的动力学。结果如下：我们证明了存活的胰腺外分泌细胞抑制末端外分泌基因程序，并诱导通常与未分化胰腺祖细胞相关的基因，如Pdx 1，E-钙粘蛋白，β-连环蛋白和Notch组分，包括Notch 1，Notch 2和Jagged 2。Notch靶基因Hes 1的表达提供了Notch信号在去分化胰腺细胞中重新激活的证据。虽然以前的研究表明胰腺再生腺泡到导管转分化的过程中，我们没有发现任何证据表明，去分化的细胞在此过程中获得导管的命运。结论：在小鼠中，化学诱导的胰腺炎后的胰腺再生主要通过腺泡细胞去分化发生，由此恢复类似于胚胎胰腺前体的遗传程序。
Background & Aims: The mammalian pancreas has a strong regenerative potential, but the origin of organ restoration is not clear, and it is not known to what degree such a process reflects pancreatic development. To define cell differentiation changes associated with pancreatic regeneration in adult mice, we compared regeneration following caerulein-induced pancreatitis to that of normal pancreatic development. Methods: By performing comparative histology for adult and embryonic pancreatic markers in caerulein-treated and control pancreas, we addressed cellular proliferation and differentiation (amylase, DBA-agglutinin, insulin, glucagon, beta-catenin, E-cadherin, Pdx1, Nkx6.1, Notch1, Notch2, Jagged1, Jagged2, Hes1), hereby describing the kinetics of tissue restoration. Results: We demonstrate that surviving pancreatic exocrine cells repress the terminal exocrine gene program and induce genes normally associated with undifferentiated pancreatic progenitor cells such as Pdx1, E-cadherin, beta-catenin, and Notch components, including Notch1, Notch2, and Jagged2. Expression of the Notch target gene Hes1 provides evidence that Notch signaling is reactivated in dedifferentiated pancreatic cells. Although previous studies have suggested a process of acino-to-ductal transdifferentiation in pancreatic regeneration, we find no evidence to suggest that dedifferentiated cells acquire a ductal fate during this process. Conclusions: Pancreatic regeneration following chemically induced pancreatitis in the mouse occurs predominantly through acinar cell dedifferentiation, whereby a genetic program resembling embryonic pancreatic precursors is reinstated.