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. Overall design: Pooled CRISPR-mediated perturbation of transcription factors in primary human hematopoietic cells, harvested at day 7, day 9, day 11 and day 14 of in vitro erythroid differentiation with single cell RNA and ATAC readouts. UPDATE: [June 05, 2025] The Sample titles were updated.