Understanding how individual cells make fate decisions that lead to the faithful formation and homeostatic maintenance of tissues is a fundamental goal of contemporary developmental and stem cell biology. Seemingly uniform populations of stem cells and multipotent progenitors display a surprising degree of heterogeneity, primarily originating from the inherent stochastic nature of molecular processes underlying gene expression. Despite this heterogeneity, lineage decisions result in tissues of a defined size and with consistent proportions of differentiated cell types. Using the early mouse embryo as a model we review recent developments that have allowed the quantification of molecular intercellular heterogeneity during cell differentiation. We first discuss the relationship between these heterogeneities and developmental cellular potential. We then review recent theoretical approaches that formalize the mechanisms underlying fate decisions in the inner cell mass of the blastocyst stage embryo. These models build on our extensive knowledge of the genetic control of fate decisions in this system and will become essential tools for a rigorous understanding of the connection between noisy molecular processes and reproducible outcomes at the multicellular level. We conclude by suggesting that cell‐to‐cell communication provides a mechanism to exploit and buffer intercellular variability in a self‐organized process that culminates in the reproducible formation of the mature mammalian blastocyst stage embryo that is ready for implantation into the maternal uterus.

中文翻译：

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利用生物噪音做出血统决定：早期小鼠胚胎的教训。

了解单个细胞如何做出命运决定，从而忠实地形成组织并保持体内稳态，这是当代发育和干细胞生物学的基本目标。看似均匀的干细胞和多能祖细胞群显示出令人惊讶的异质性程度，这主要源自基因表达所基于的分子过程的固有随机性。尽管存在这种异质性，谱系决定仍会导致组织具有确定的大小，并具有一致比例的分化细胞类型。使用早期小鼠胚胎作为模型，我们回顾了最近的发展，这些发展已允许量化细胞分化过程中的分子间异质性。我们首先讨论这些异质性与发育细胞潜力之间的关系。然后，我们回顾了最近的理论方法，这些方法正规化了胚泡期胚胎内细胞团中命运决定的机制。这些模型建立在我们对系统中命运决定的遗传控制的广泛了解的基础上，将成为在多细胞水平上严格理解嘈杂的分子过程与可再现结果之间联系的必不可少的工具。我们的结论是，细胞间通讯提供了一种机制，可以利用和缓冲自组织过程中的细胞间变异性，最终形成可重复形成的成熟哺乳动物胚泡期胚胎，并准备将其植入母体子宫。