Delacour Alexandra, Nepote Virginie, Trumpp Andreas, Herrera Pedro Luis
Department of Morphology, room 5040, University of Geneva Medical School, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.
Mech Dev. 2004 Jan;121(1):3-14. doi: 10.1016/j.mod.2003.11.004.
Expression of nestin has been suggested to be a characteristic of pancreatic islet stem cells. To determine whether nestin is indeed expressed in such putative cells during embryonic development, or in the adult pancreas after injury, we performed a cell lineage analysis using two independent lines of transgenic mice encoding Cre recombinase under the control of rat nestin cis-regulatory sequences, each crossed with loxP-bearing R26R mice. F1 animals produced the reporter molecule beta-galactosidase only upon Cre-mediated recombination, thus solely in cells using (or having used) the transgenic nestin promoter. In early pancreatic primordia, beta-galactosidase was observed in mesenchymal and epithelial cells. At later developmental stages or in adults, vast clusters of acinar cells and few ductal cells were labeled, in addition to fibroblasts and vascular cells, but no endocrine cells were tagged by beta-galactosidase. This correlated with the transient expression, observed with an anti-nestin antibody, of endogenous nestin in about 5% of epithelial cells during development (whether in cord-forming arrangements or in nascent acini), and in vascular and mesenchymal structures. After partial pancreatectomy, there was a transient increase of the number of anti-nestin-labeled endothelial cells, but again, no endocrine cells bore beta-galactosidase. Together, these findings show that nestin is expressed in the pancreatic exocrine cell lineage, and suggest that consistent nestin expression is not a major feature of islet endocrine progenitor cells.
巢蛋白的表达已被认为是胰岛干细胞的一个特征。为了确定在胚胎发育过程中巢蛋白是否确实在这类假定的细胞中表达，或者在成年胰腺损伤后是否表达，我们使用了两个独立品系的转基因小鼠进行细胞谱系分析，这些小鼠在大鼠巢蛋白顺式调控序列的控制下编码Cre重组酶，每个品系都与携带loxP的R26R小鼠杂交。F1代动物仅在Cre介导的重组后产生报告分子β-半乳糖苷酶，因此仅在使用（或已经使用）转基因巢蛋白启动子的细胞中产生。在胰腺原基早期，在间充质和上皮细胞中观察到β-半乳糖苷酶。在发育后期或成年期，除了成纤维细胞和血管细胞外，大量腺泡细胞簇和少数导管细胞被标记，但没有内分泌细胞被β-半乳糖苷酶标记。这与用抗巢蛋白抗体观察到的内源性巢蛋白在发育过程中约5%的上皮细胞（无论是在形成索状排列还是在新生腺泡中）以及血管和间充质结构中的瞬时表达相关。部分胰腺切除术后，抗巢蛋白标记内皮细胞的数量短暂增加，但同样，没有内分泌细胞携带β-半乳糖苷酶。总之，这些发现表明巢蛋白在胰腺外分泌细胞谱系中表达，并表明持续的巢蛋白表达不是胰岛内分泌祖细胞的主要特征。
