Intraislet Pancreatic Ducts Can Give Rise to Insulin-Positive Cells
Intraislet Pancreatic Ducts Can Give Rise to Insulin-Positive Cells
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DOI：
10.1210/en.2015-1175
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发表时间：
2016-01-01
期刊：
影响因子：
4.8
通讯作者：
Gittes, George K.
中科院分区：
文献类型：
--
作者：
El-Gohary, Yousef;Wiersch, John;Gittes, George K.
糖尿病研究中的一个关键问题是新的β细胞能否从内源性非内分泌细胞中产生。胰腺导管细胞转化为β细胞的可能性是一个备受争议的问题。到目前为止，尚不清楚是什么解剖过程导致导管衍生细胞在先前存在的胰岛中存在。我们使用全挂载技术直接观察了年轻野生型小鼠、年轻人类、野生型和转基因小鼠在部分胰腺切除术后的胰腺导管网络。在幼鼠和人类中发现起源于主导管树的胰腺导管网络存在于胰岛深处，但在成年小鼠和人类中没有发现。这些网络在部分胰腺切除术后的正常成年小鼠中也不存在，但tgf - β受体突变小鼠在部分胰腺切除术后显示出这些胰岛内管结构的形成。遗传和病毒谱系追踪用于确定内分泌细胞是否来源于胰管。谱系追踪证实，胰腺导管细胞在正常的年轻发育小鼠以及在部分胰腺切除术后tgf - β信号突变的成年小鼠中通常可以转化为新的β细胞。这里的直接视觉证据表明，胰腺导管生长成胰岛，以及谱系追踪，不仅是出生后胰腺导管细胞产生β细胞的有力证据，而且重要的是暗示了tgf - β信号在这一过程中。
A key question in diabetes research is whether new beta-cells can be derived from endogenous, nonendocrine cells. The potential for pancreatic ductal cells to convert into beta-cells is a highly debated issue. To date, it remains unclear what anatomical process would result in duct-derived cells coming to exist within preexisting islets. We used a whole-mount technique to directly visualize the pancreatic ductal network in young wild-type mice, young humans, and wild-type and transgenic mice after partial pancreatectomy. Pancreatic ductal networks, originating from the main ductal tree, were found to reside deep within islets in young mice and humans but not in mature mice or humans. These networks were also not present in normal adult mice after partial pancreatectomy, but TGF-beta receptor mutant mice demonstrated formation of these intraislet duct structures after partial pancreatectomy. Genetic and viral lineage tracings were used to determine whether endocrine cells were derived from pancreatic ducts. Lineage tracing confirmed that pancreatic ductal cells can typically convert into new beta-cells in normal young developing mice as well as in adult TGF-beta signaling mutant mice after partial pancreatectomy. Here the direct visual evidence of ducts growing into islets, along with lineage tracing, not only represents strong evidence for duct cells giving rise to beta-cells in the postnatal pancreas but also importantly implicates TGF-beta signaling in this process.