近日，美国白头生物医学研究所Iain M. Cheeseman等研究人员合作绘制出人类必需基因的表型图谱。相关论文于2022年11月7日在线发表在《细胞》杂志上。
研究人员将基于CRISPR-Cas9的人类HeLa细胞中5072个基因的功能筛选与基于显微镜的DNA、DNA损伤反应、肌动蛋白和微管的成像相结合。对超过3100万个单个细胞的分析确定了超过90%的基因敲除的可测量表型，并提示了特定细胞过程中的基因靶标。基于数百个定量参数的表型相似性聚类，研究人员进一步揭示了跨越不同细胞活动的共同功能基因，并提供了对基因功能和关联的预测。
通过对239个基因的45万个细胞分裂事件进行集合活细胞筛选，研究人员还发现了对染色体分离有功能贡献的不同基因。这项工作建立了一个资源，其详细说明了破坏核心细胞过程的后果，而且代表了人类必需基因的功能图谱。
据介绍，了解细胞生长、增殖和功能的基础需要确定必需基因在不同细胞过程中的作用，包括可视化它们对细胞组织和形态学的贡献。
附：英文原文
Title: The phenotypic landscape of essential human genes
Author: Luke Funk, Kuan-Chung Su, Jimmy Ly, David Feldman, Avtar Singh, Brittania Moodie, Paul C. Blainey, Iain M. Cheeseman
Issue&Volume: 2022-11-07
Abstract: Understanding the basis for cellular growth, proliferation, and function requiresdetermining the roles of essential genes in diverse cellular processes, includingvisualizing their contributions to cellular organization and morphology. Here, wecombined pooled CRISPR-Cas9-based functional screening of 5,072 fitness-conferringgenes in human HeLa cells with microscopy-based imaging of DNA, the DNA damage response,actin, and microtubules. Analysis of >31 million individual cells identified measurablephenotypes for >90% of gene knockouts, implicating gene targets in specific cellularprocesses. Clustering of phenotypic similarities based on hundreds of quantitativeparameters further revealed co-functional genes across diverse cellular activities,providing predictions for gene functions and associations. By conducting pooled live-cellscreening of ～450,000 cell division events for 239 genes, we additionally identifieddiverse genes with functional contributions to chromosome segregation. Our work establishesa resource detailing the consequences of disrupting core cellular processes that representsthe functional landscape of essential human genes.
DOI: 10.1016/j.cell.2022.10.017
Source: https://www.cell.com/cell/fulltext/S0092-8674(22)01359-9
来源：科学网 小柯机器人