小柯机器人

美国加州大学旧金山分校Alex A. Pollen等研究人员合作绘制出人类和黑猩猩干细胞中遗传依赖性的比较图谱。相关论文于2023年6月20日在线发表在《细胞》杂志上。

研究人员建立了一个比较功能缺失的方法来评估人类细胞是否表现出不同的遗传依赖性。通过在人类和黑猩猩多能干细胞中进行全基因组CRISPR干扰筛选，研究人员确定了75个对细胞增殖具有物种特异性影响的基因。这些基因由连贯的过程组成，包括细胞周期进展和溶酶体信号，通过与猩猩细胞的比较，研究人员确定这些基因来自于人类。在神经祖细胞和脑器官中，人类对CDK2和CCNE1缺乏的特异性稳健性持续存在，支持G1期长度假说作为人类大脑扩张的一个潜在演化机制。这些研究结果表明，人类细胞的演化改变重塑了基本基因的景观，并建立了一个系统地揭示物种间潜在细胞和分子差异的平台。

据悉，对类人猿的比较研究为了解人类的演化史提供了一个窗口，但在人类演化过程中出现的细胞差异的程度和特性在很大程度上仍未得到探索。

附：英文原文

Title: Comparative landscape of genetic dependencies in human and chimpanzee stem cells

Author: Richard She, Tyler Fair, Nathan K. Schaefer, Reuben A. Saunders, Bryan J. Pavlovic, Jonathan S. Weissman, Alex A. Pollen

Issue&Volume: 2023-06-20

Abstract: Comparative studies of great apes provide a window into our evolutionary past, but the extent and identity of cellular differences that emerged during hominin evolution remain largely unexplored. We established a comparative loss-of-function approach to evaluate whether human cells exhibit distinct genetic dependencies. By performing genome-wide CRISPR interference screens in human and chimpanzee pluripotent stem cells, we identified 75 genes with species-specific effects on cellular proliferation. These genes comprised coherent processes, including cell-cycle progression and lysosomal signaling, which we determined to be human-derived by comparison with orangutan cells. Human-specific robustness to CDK2 and CCNE1 depletion persisted in neural progenitor cells and cerebral organoids, supporting the G1-phase length hypothesis as a potential evolutionary mechanism in human brain expansion. Our findings demonstrate that evolutionary changes in human cells reshaped the landscape of essential genes and establish a platform for systematically uncovering latent cellular and molecular differences between species.

DOI: 10.1016/j.cell.2023.05.043

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)00595-0