Golov Arkadiy K, Razin Sergey V, Gavrilov Alexey A
Institute of Gene Biology of the Russian Academy of Sciences, Vavilov Street 34/5, Moscow, Russia, 119334.
Molecular Biology Department, Biological Faculty, Lomonosov Moscow State University, Moscow, Russia, 119992.
Histochem Cell Biol. 2016 Sep;146(3):239-54. doi: 10.1007/s00418-016-1466-z. Epub 2016 Jul 13.
Huge numbers of cells form an adult animal body, ranging from several thousands in Placozoa and small nematodes to many billions in mammals. Cells are classified into separate groups known as cell types by their morphological and biochemical features. Six to several hundreds of spatially ordered cell types are recognized in different animals. This complex organization develops from one cell, a zygote, during ontogeny, and its dynamic equilibrium is often maintained in the adult body. One of the key challenges in biology is to understand the mechanisms that sustain the reproducible development of a complex ordered cell ensemble such as the animal body from a single cell. How cells with identical genomes stably maintain one of the numerous possible phenotypes? How the cell differentiation lineage is selected during development? What genes play a key role in maintaining cell identity, and how do they determine expression of other genes characteristic of the relevant cell type? How does the basically stochastic nature of transcription in an isolated cell affect the stability of cell identity, the selection of a cell lineage, and the variability of cell responses to external stimuli? Better-grounded answers to these questions have become possible with recent progress in single-cell genome-wide analysis techniques, which combine the high throughput of biochemical methods and the differential nature of microscopy. The techniques are still in their infancy, and their further development will certainly revolutionize many fields of life sciences and, in particular, developmental biology. Here, we summarize the main results that have been obtained in single-cell genome-wide analyses and describe the nongenetic cell-to-cell variability in animals.
大量细胞构成了成年动物体，从扁盘动物和小型线虫中的数千个细胞到哺乳动物中的数十亿个细胞不等。细胞根据其形态和生化特征被分类为不同的组，即细胞类型。在不同动物中可识别出6到数百种空间有序的细胞类型。这种复杂的组织在个体发育过程中从一个细胞——受精卵发育而来，并且其动态平衡在成年动物体内通常得以维持。生物学中的一个关键挑战是理解从单个细胞维持诸如动物体这样复杂有序的细胞集合的可重复发育的机制。具有相同基因组的细胞如何稳定地维持众多可能表型中的一种？在发育过程中细胞分化谱系是如何被选择的？哪些基因在维持细胞身份方面起关键作用，以及它们如何决定相关细胞类型特有的其他基因的表达？孤立细胞中转录的基本随机性如何影响细胞身份的稳定性、细胞谱系的选择以及细胞对外部刺激反应的变异性？随着单细胞全基因组分析技术的最新进展，对这些问题有了更有依据的答案，这些技术结合了生化方法的高通量和显微镜的差异性。这些技术仍处于起步阶段，它们的进一步发展必将彻底改变生命科学的许多领域，尤其是发育生物学。在这里，我们总结了单细胞全基因组分析中获得的主要结果，并描述了动物细胞间的非遗传变异性。
