美国莫里奇研究所Jason R. Cantor和蒙塔尼生物医学研究所David M. Sabatini研究组合作取得一项新突破。他们通过在生理介质中进行CRISPR筛选揭示了人细胞中的条件性必需基因。该研究于2021年3月1日在线发表于国际学术期刊《细胞-代谢》杂志。

在本研究中，研究人员在普通与人血浆样培养基（HPLM）中进行了CRISPR筛选。人癌细胞系中的条件必需基因簇跨多个细胞过程，并随自然细胞内在多样性以及培养基基础成分和血清成分的组合而变化。值得注意的是，研究人员追踪了三种条件性CRISPR表型产生的原因，并最终归因于HPLM与传统培养基特异代谢物的可用性差异。

该发现揭示了培养基成分对人细胞中基因必需性的深远影响，并提出了在HPLM中使用遗传筛选发现新的癌症易感基因和基因-营养物相互作用的一般策略。

据介绍，跨数百种癌细胞系的基因筛选已确定增殖性人细胞中的遗传依赖性以及它们如何随基因型和谱系而变化。但是，大多数筛选是在不完全包涵人血液代谢物的培养基中进行。

附：英文原文

Title: CRISPR screens in physiologic medium reveal conditionally essential genes in human cells

Author: Nicholas J. Rossiter, Kimberly S. Huggler, Charles H. Adelmann, Heather R. Keys, Ross W. Soens, David M. Sabatini, Jason R. Cantor

Issue&Volume: 2021-03-01

Abstract: Forward genetic screens across hundreds of cancer cell lines have started to definethe genetic dependencies of proliferating human cells and how these vary by genotypeand lineage. Most screens, however, have been carried out in culture media that poorlyreflect metabolite availability in human blood. Here, we performed CRISPR-based screensin traditional versus human plasma-like medium (HPLM). Sets of conditionally essentialgenes in human cancer cell lines span several cellular processes and vary with bothnatural cell-intrinsic diversity and the combination of basal and serum componentsthat comprise typical media. Notably, we traced the causes for each of three conditionalCRISPR phenotypes to the availability of metabolites uniquely defined in HPLM versusconventional media. Our findings reveal the profound impact of medium compositionon gene essentiality in human cells, and also suggest general strategies for usinggenetic screens in HPLM to uncover new cancer vulnerabilities and gene-nutrient interactions.

DOI: 10.1016/j.cmet.2021.02.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00061-9