Barbara Davis Center for Childhood Diabetes, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Pancreas. 2012 Aug;41(6):962-9. doi: 10.1097/MPA.0b013e31823d0160.
This study investigated the utility of advanced computational techniques to large-scale genome-based data to identify novel genes that govern murine pancreatic development.
An expression data set for mouse pancreatic development was complemented with high-throughput data analyzer to identify and prioritize novel genes. Quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry were used to validate selected genes.
Four new genes whose roles in the development of murine pancreas have not previously been established were identified: cystathionine β-synthase (Cbs), Meis homeobox 1, growth factor independent 1, and aldehyde dehydrogenase 18 family, member A1. Their temporal expression during development was documented. Cbs was localized in the cytoplasm of the tip cells of the epithelial chords of the undifferentiated progenitor cells at E12.5 and was coexpressed with the pancreatic and duodenal homeobox 1 and pancreas-specific transcription factor, 1a-positive cells. In the adult pancreas, Cbs was localized primarily within the acinar compartment.
In silico analysis of high-throughput microarray data in combination with background knowledge about genes provides an additional reliable method of identifying novel genes. To our knowledge, the expression and localization of Cbs have not been previously documented during mouse pancreatic development.
本研究利用先进的计算技术对基于基因组的大规模数据进行分析，以鉴定调控小鼠胰腺发育的新基因。
利用高通量数据分析器补充小鼠胰腺发育的表达数据集，以识别和优先考虑新基因。采用实时定量聚合酶链反应、原位杂交和免疫组织化学方法对选定的基因进行验证。
鉴定出 4 个新基因，它们在小鼠胰腺发育中的作用以前尚未确定：胱硫醚β-合酶（Cbs）、Meis 同源盒 1、生长因子独立 1 和醛脱氢酶 18 家族成员 A1。记录了它们在发育过程中的时间表达。Cbs 在 E12.5 的未分化祖细胞的上皮索的顶端细胞的细胞质中定位，与胰腺十二指肠同源盒 1 和胰腺特异性转录因子 1a 阳性细胞共表达。在成年胰腺中，Cbs 主要定位于腺泡区。
通过计算分析高通量微阵列数据并结合有关基因的背景知识，为鉴定新基因提供了一种额外的可靠方法。据我们所知，Cbs 的表达和定位在小鼠胰腺发育过程中以前尚未被记录。
