Profiling of embryonic stem cell differentiation.
Profiling of embryonic stem cell differentiation.
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DOI：
10.1900/rds.2014.11.102
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发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
Kume, Shoen
中科院分区：
文献类型：
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作者：
Shiraki, Nobuaki;Ogaki, Soichiro;Kume, Shoen
胚胎干 (ES) 细胞已被证明能够重现正常的发育阶段。因此，它们是发育生物学研究中非常有用的工具。 ES 细胞衍生细胞的分析获得了有关分化细胞特征的重要信息，并允许鉴定新的标记基因和分化途径。在这篇综述中，我们重点关注几个研究小组对小鼠胚胎、人类胰岛和人类 ES 细胞衍生的分化细胞进行分析研究的最新结果。来自小鼠胚胎的全局基因表达数据已被用来识别发育过程中涉及的新基因或途径，并寻找调节直接重编程的转录因子。我们介绍了人类胰腺细胞的基因表达数据库（Beta Cell Gene Atlas、EuroDia 数据库），并总结了胰岛细胞或人类 ES 细胞来源的胰腺细胞的分析研究，重点关注基因表达、microRNA、表观遗传学和蛋白质表达。然后，我们描述了我们的基因表达谱分析以及我们对新型内胚层或胰腺祖细胞标记基因的搜索。我们将小鼠 ES 细胞分化为中内胚层、定形内胚层 (DE)、中胚层、外胚层和表达 Pdx1 的胰腺谱系，并进行 DNA 微阵列分析。提取在DE和/或表达Pdx1的细胞中特异性表达的基因，并通过原位杂交研究它们在正常胚胎发育中的表达模式。在检查的 54 个基因中，27 个在 E8.5 小鼠胚胎的 DE 中表达，15 个基因在 E14.5 小鼠胚胎胰芽的不同结构域中表达。 Akr1c19、Aebp2、Pbxip1 和 Creb3l1 都是新的，并且没有被描述为在 DE 或胰腺中表达。通过介绍ES细胞来源的细胞的分析结果，将讨论使用ES细胞研究早期胚胎发育的好处。
Embryonic stem (ES) cells have been shown to recapitulate normal developmental stages. They are therefore a highly useful tool in the study of developmental biology. Profiling of ES cell-derived cells has yielded important information about the characteristics of differentiated cells, and allowed the identification of novel marker genes and pathways of differentiation. In this review, we focus on recent results from profiling studies of mouse embryos, human islets, and human ES cell-derived differentiated cells from several research groups. Global gene expression data from mouse embryos have been used to identify novel genes or pathways involved in the developmental process, and to search for transcription factors that regulate direct reprogramming. We introduce gene expression databases of human pancreas cells (Beta Cell Gene Atlas, EuroDia database), and summarize profiling studies of islet- or human ES cell-derived pancreatic cells, with a focus on gene expression, microRNAs, epigenetics, and protein expression. Then, we describe our gene expression profile analyses and our search for novel endoderm, or pancreatic, progenitor marker genes. We differentiated mouse ES cells into mesendoderm, definitive endoderm (DE), mesoderm, ectoderm, and Pdx1-expressing pancreatic lineages, and performed DNA microarray analyses. Genes specifically expressed in DE, and/or in Pdx1-expressing cells, were extracted and their expression patterns in normal embryonic development were studied by in situ hybridization. Out of 54 genes examined, 27 were expressed in the DE of E8.5 mouse embryos, and 15 genes were expressed in distinct domains in the pancreatic buds of E14.5 mouse embryos. Akr1c19, Aebp2, Pbxip1, and Creb3l1 were all novel, and none has been described as being expressed, either in the DE, or in the pancreas. By introducing the profiling results of ES cell-derived cells, the benefits of using ES cells to study early embryonic development will be discussed.