Transcription factor networks disproportionately enrich for heritability of blood cell phenotypes [PRO-Seq]

We developed a strategy to couple highly-efficient pooled CRISPR-mediated perturbation of key master hematopoietic transcription factors in differentiating primary human hematopoietic cells with joint single-cell gene expression and chromatin accessibility profiling to enable the reconstruction of transcription factor-dependent gene regulatory networks throughout primary hematopoietic differentiation. Overall design: CRISPR/Cas9-mediated editing of AAVS1 or GATA1 locus in primary erythroblasts at day 8 of differentiation. 24h after editing, cells underwent precision nuclear run-on (PRO-seq).