2017年1月30日,国际核酸类重要学术期刊《Nucleic Acids Research》杂志在线发表了中国科学院广州生物医药与健康研究所裴端卿研究组和南方科技大学生物系Andrew Hutchins课题组合作的一篇研究论文,论文题为“Models of global gene expression define major domains of cell type and tissue identity”。Andrew Hutchins研究员为论文通讯作者。
诸如实验鼠和人等复杂动物基本上为三个胚层的生物体:由内层(内胚层)、中层(中胚层)和外层(外胚层)构成。这三个胚层在胚胎发育的早期就已形成,并会构成完整生物体的不同组织。例如,内胚层将继续形成内部器官,例如肝脏和肠。 中胚层形成中间组织,例如心脏和肌肉,而外胚层形成外部组织,例如皮肤和大脑。
这三层结构传统上通过仔细的形态学观察、解剖学观察和实验来定义。Andrew Hutchins教授及其组员的研究是用计算机学方法来重新定义这三层结构。通过利用近1000 个rna-seq基因表达样本(涵盖272个组织),构建三层结构的计算机模型。这些模型可准确复原这三个已知胚层:内胚层、中胚层和外胚层以及早期胚胎细胞。有趣的是,他们的模型还表明其他层结构的存在:免疫系统(血液中胚层)、下颌及面部结构(神经嵴)和皮肤(表面外胚层)。
此外,他们发现控制每个层的“主调节器”基因,这些基因可以阻止细胞在域之间转化。这些模型有助于理解干细胞的分化转移、发育细胞生物学和再生医学。
原文摘要:The current classification of cells in an organism is largely based on their anatomic and developmental origin. Cells types and tissues are traditionally classified into those that arise from the three embryonic germ layers, the ectoderm, mesoderm and endoderm, but this model does not take into account the organization of cell type-specific patterns of gene expression. Here, we present computational models for cell type and tissue specification derived from a collection of 921 RNA-sequencing samples from 272 distinct mouse cell types or tissues. In an unbiased fashion, this analysis accurately predicts the three known germ layers. Unexpectedly, this analysis also suggests that in total there are eight major domains of cell type-specification, corresponding to the neurectoderm, neural crest, surface ectoderm, endoderm, mesoderm, blood mesoderm, germ cells and the embryonic domain. Further, we identify putative genes responsible for specifying the domain and the cell type. This model has implications for understanding trans-lineage differentiation for stem cells, developmental cell biology and regenerative medicine.