Figure 3. Mapping cis- and trans-regulatory target genes of proliferation-modifying hDels.

a, Single-cell CRISPRi screening approach (hDel-v3).

b, Differential gene expression for cells ('pseudobulk') harboring the indicated transcription start site-targeting sgRNA (*FDR < 0.1).

c, Distributions of observed and expected (uniform) p-values for cis differential expression for hDel-targeting sgRNA-gene pairs (orange) and non-targeting sgRNA-gene pairs (gray, downsampled). Blue line: observed p-value = expected p-value.

d, hDel_6012-targeting sgRNA log₂ fold-change (hDel-v2; gold, FDR < 0.05) and RPL26 Omni-ATAC seq, H3K4me1, H3K4me3, and H3K27ac in C3624K.

e, Differential RPL26 expression for cells harboring the indicated hDel_6012-targeting sgRNA (*FDR < 0.1).

f, Scatterplot of hDel_6012-targeting sgRNA log₂ fold-change (cellular proliferation, hDel-v2) and RPL26 log₂ fold-change (gene expression, hDel-v3).

g, trans differential expression for cells harboring hDel_6012-targeting sgRNAs (gene log₂ fold-change and Benjamini-Hochberg-adjusted p-value). Green: cis target gene; orange: ribosomal genes (FDR < 0.1).

h, hDel_6304-targeting sgRNA log₂ fold-change (hDel-v2; gold, FDR < 0.05) and MBD3 Omni-ATAC seq, H3K4me1, H3K4me3, and H3K27ac in C3624K.

i, Differential MBD3 expression for cells harboring the indicated hDel_6304-targeting sgRNA (*FDR < 0.1).

j, Scatterplot of hDel_6304-targeting sgRNA log₂ fold-change (cellular proliferation, hDel-v2) and MBD3 log₂ fold-change (gene expression, hDel-v3).

k, trans differential expression for cells harboring hDel_6304-targeting sgRNAs (gene log₂ fold-change and Benjamini-Hochberg-adjusted p-value). Green: cis target gene; orange: meso-endoderm (FDR < 0.1).