我们的祖先获得了形态、认知和代谢变化，使人类能够在多样的栖息地中定居，发展出非凡的技术，并重塑生物圈。了解这些变化的遗传、发育和分子基础，将有助于揭示我们成为人类的本质。由于存在大量低效基因变化，缺乏细胞类型水平上的发育时期现象差异的描述以及实验模型的缺乏，将人类特定的基因变化与物种差异相连接一直是一个挑战。现在，单细胞测序、遗传操作和干细胞培养等新兴方法已支持对具有人类或猿类基因背景的定义细胞类型进行描述性和功能研究。在本综述中，我们描述了从现代和古代人类、大猩猩和其他灵长类动物的基因组测序中发现人类特有的基因变化，以及新的分子和细胞方法 - 包括细胞图谱和器官样本 - 如何使探索潜在的因果因素，这些因素是人类特有特征的基础。 © 2023. Springer Nature Limited.

Our ancestors acquired morphological, cognitive and metabolic modifications that enabled humans to colonize diverse habitats, develop extraordinary technologies and reshape the biosphere. Understanding the genetic, developmental and molecular bases for these changes will provide insights into how we became human. Connecting human-specific genetic changes to species differences has been challenging owing to an abundance of low-effect size genetic changes, limited descriptions of phenotypic differences across development at the level of cell types and lack of experimental models. Emerging approaches for single-cell sequencing, genetic manipulation and stem cell culture now support descriptive and functional studies in defined cell types with a human or ape genetic background. In this Review, we describe how the sequencing of genomes from modern and archaic hominins, great apes and other primates is revealing human-specific genetic changes and how new molecular and cellular approaches - including cell atlases and organoids - are enabling exploration of the candidate causal factors that underlie human-specific traits.© 2023. Springer Nature Limited.