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.

我们开发了一种名为Perturb-Multiome的研究策略，可将原代人类造血细胞分化进程中，混合CRISPR文库介导的核心转录因子高效扰动，与联合单细胞基因表达谱及染色质可及性谱分析进行整合耦联。该策略可实现造血分化全过程中依赖于转录因子的基因调控网络的重构。最终，我们整合了全基因组关联研究（Genome-Wide Association Study, GWAS）数据集，探究由上述已鉴定的转录因子调控网络所解释的血液表型遗传力。整体实验设计：在原代人类造血细胞中通过混合CRISPR文库介导转录因子扰动，于体外红系分化的第7、9、11及14天收集样本，并开展单细胞RNA测序与ATAC测序检测。更新说明：[2025年6月5日] 样本标题已更新。