生物
细胞凋亡
清脆的
DNA
细胞生物学
基因
调解人
核糖核酸
细胞
胎儿游离DNA
细胞培养
计算生物学
分子生物学
遗传学
怀孕
胎儿
产前诊断
作者
Brad A Davidson,Adam X. Miranda,Sarah C. Reed,Riley E. Bergman,Justin Kemp,Anvith P. Reddy,Morgan V. Pantone,Emily B. Fox,Rodney Dixon Dorand,Paula J. Hurley,Sarah Croessmann,Ben Ho Park
标识
DOI:10.1038/s42003-024-06129-1
摘要
Clinical circulating cell-free DNA (cfDNA) testing is now routine, however test accuracy remains limited. By understanding the life-cycle of cfDNA, we might identify opportunities to increase test performance. Here, we profile cfDNA release across a 24-cell line panel and utilize a cell-free CRISPR screen (cfCRISPR) to identify mediators of cfDNA release. Our panel outlines two distinct groups of cell lines: one which releases cfDNA fragmented similarly to clinical samples and purported as characteristic of apoptosis, and another which releases larger fragments associated with vesicular or necrotic DNA. Our cfCRISPR screens reveal that genes mediating cfDNA release are primarily involved with apoptosis, but also identify other subsets of genes such as RNA binding proteins as potential regulators of cfDNA release. We observe that both groups of cells lines identified primarily produce cfDNA through apoptosis. These results establish the utility of cfCRISPR, genetically validate apoptosis as a major mediator of DNA release in vitro, and implicate ways to improve cfDNA assays.
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