Transcription factor networks disproportionately enrich for heritability of blood cell phenotypes [10x ATAC + GEX Multiome]

We developed a strategy (Perturb-Multiome) to couple highly-efficient pooled CRISPR-mediated perturbation of master transcription factors in differentiating primary human hematopoietic cells with joint single-cell gene expression and chromatin accessibility profiling. This approach enabled the reconstruction of transcription factor-dependent gene regulatory networks throughout hematopoietic differentiation. Ultimately, we integrated GWAS datasets to explore the heritability of blood phenotypes explained by these identified transcription-factor regulatory networks.