Modest increase of KIF11 expression exposes fragilities in the mitotic spindle, causing chromosomal instability.

ABSTRACT: Chromosomal instability (CIN), the process of increased chromosomal alterations, compromises genomic integrity and has profound consequences on human health. Yet, our understanding of the molecular and mechanistic basis of CIN initiation remains limited. We developed a high-throughput, single-cell, image-based pipeline employing deep-learning and spot-counting models to detect CIN by automatically counting chromosomes and micronuclei. To identify CIN-initiating conditions, we used CRISPR activation in human diploid cells to upregulate, at physiologically relevant levels, 14 genes that are functionally important in cancer. We found that upregulation of CCND1, FOXA1 and NEK2 resulted in pronounced changes in chromosome counts, and KIF11 upregulation resulted in micronuclei formation. We iden

SUBMITTER: Dale KL 

PROVIDER: S-EPMC10500341 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature