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Cell-type and dynamic state govern genetic regulation of gene expression in heterogeneous differentiating cultures

ABSTRACT: Identifying the molecular effects of human genetic variation across cellular contexts is crucial for understanding the mechanisms underlying disease-associated loci, yet many cell-types and developmental stages remain underexplored. Here we harnessed the potential of heterogeneous differentiating cultures (HDCs), anin vitrosystem in which pluripotent cells asynchronously differentiate into a broad spectrum of cell-types. We generated HDCs for 53 human donors and collected single-cell RNA-sequencing data from over 900,000 cells. We identified expression quantitative trait loci in 29 cell-types and characterized regulatory dynamics across diverse differentiation trajectories.This revealed novel regulatory variants for genes involved in key developmental and disease-related processes while replicating known effects from primary tissues, and dynamic regulatory effects associated with a range of complex traits.

ORGANISM(S): Homo sapiens

PROVIDER: GSE266500 | GEO | 2024/07/15

REPOSITORIES: GEO

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