Gu Guoqiang, Wells James M, Dombkowski David, Preffer Fred, Aronow Bruce, Melton Douglas A
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Development. 2004 Jan;131(1):165-79. doi: 10.1242/dev.00921. Epub 2003 Dec 3.
To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles of enriched cells isolated from four biologically significant stages of endocrine pancreas development: endoderm before pancreas specification, early pancreatic progenitor cells, endocrine progenitor cells and adult islets of Langerhans. These analyses implicate new signaling pathways in endocrine pancreas development, and identified sets of known and novel genes that are temporally regulated, as well as genes that spatially define developing endocrine cells from their neighbors. The differential expression of several genes from each time point was verified by RT-PCR and in situ hybridization. Moreover, we present preliminary functional evidence suggesting that one transcription factor encoding gene (Myt1), which was identified in our screen, is expressed in endocrine progenitors and may regulate alpha, beta and delta cell development. In addition to identifying new genes that regulate endocrine cell fate, this global gene expression analysis has uncovered informative biological trends that occur during endocrine differentiation.
为了定义调节内分泌胰腺发育的基因通路，我们生成了从内分泌胰腺发育的四个生物学重要阶段分离出的富集细胞的转录谱：胰腺特化前的内胚层、早期胰腺祖细胞、内分泌祖细胞和成年朗格汉斯胰岛。这些分析揭示了内分泌胰腺发育中的新信号通路，并鉴定了一组在时间上受到调控的已知和新基因，以及从其相邻细胞在空间上定义发育中的内分泌细胞的基因。通过逆转录聚合酶链反应（RT-PCR）和原位杂交验证了每个时间点几个基因的差异表达。此外，我们提供了初步的功能证据，表明我们在筛选中鉴定出的一个转录因子编码基因（Myt1）在内分泌祖细胞中表达，并可能调节α、β和δ细胞的发育。除了鉴定调节内分泌细胞命运的新基因外，这种全局基因表达分析还揭示了内分泌分化过程中出现的信息丰富的生物学趋势。
