该课题组人员通过比较来自人类、黑猩猩和小鼠的组织和类器官来研究发育中的人类肠道中细胞类型的进化。该团队发现灵长类动物最近的变化与免疫屏障功能和脂质/异种代谢有关，并且人类特有的遗传特征影响这些功能。增强子分析、基因缺失和硅诱变解决了乳糖酶（LCT）和胰岛素样生长因子结合蛋白2 （IGFBP2）的进化显著增强子。总之，研究小组确定了发育中的人类肠上皮是一个快速进化的系统，并表明类人猿类器官为人类生物学提供了见解。
据了解，饮食、微生物群和其他暴露使肠上皮成为下一个发生进化变化的层；然而，人们对与适应独特人类环境相关的基因组变化知之甚少。
附：英文原文
Title: Recent evolution of the developing human intestine affects metabolic and barrier functions
Author: Qianhui Yu, Umut Kilik, Stefano Secchia, Lukas Adam, Yu-Hwai Tsai, Christiana Fauci, Jasper Janssens, Charlie J. Childs, Katherine D. Walton, Rubén López-Sandoval, Angeline Wu, Marina Almató Bellavista, Sha Huang, Calen A. Steiner, Yannick Throm, Michael James Boyle, Zhisong He, Joep Beumer, Barbara Treutlein, Craig B. Lowe, Jason R. Spence, J. Gray Camp
Issue&Volume: 2025-07-17
Abstract: Diet, microbiota, and other exposures place the intestinal epithelium as a nexus for evolutionary change; however, little is known about genomic changes associated with adaptation to a uniquely human environment. Here, we interrogate the evolution of cell types in the developing human intestine by comparing tissue and organoids from humans, chimpanzees, and mice. We find that recent changes in primates are associated with immune barrier function and lipid/xenobiotic metabolism, and that human-specific genetic features impact these functions. Enhancer assays, genetic deletion, and in silico mutagenesis resolve evolutionarily significant enhancers of Lactase (LCT) and Insulin-like Growth Factor Binding Protein 2 (IGFBP2). Altogether, we identify the developing human intestinal epithelium as a rapidly evolving system, and show that great ape organoids provide insight into human biology.
DOI: adr8628
Source: https://www.science.org/doi/10.1126/science.adr8628