Differential effects of aneuploidy on growth and differentiation in human intestinal stem cells

Aneuploidy, a near ubiquitous genetic feature of tumors, is a context-dependent driver of cancer evolution, but the mechanistic basis of this role remains unclear. By inducing heterogeneous aneuploidy in non-transformed human colon organoids (colonoids), we investigate how the effects of aneuploidy on cell growth and differentiation may promote malignant transformation. Here, we use single-cell RNA sequencing to identify the karyotype heterogenous aneuploid cells and analyze their gene expression. Overall design: Human colonoids were treated with 0.05% DMSO or 0.5 µM reversine for 24 hours followed by proliferation media for 24 hours. Colonoids were then dissociated to single cells and sequenced.