Figure 3.

Female AT2 cells have over 200 X-linked genes that escape XCI

(A) Schematic diagram showing mouse mating strategy to generate F1 mus/cast female mice with skewed XCI. In these mice, the maternal X (C57BL/6) carries the Xist deletion and is the active X (Xa), and the paternal X is always inactivated (Xi) and expresses Xist. We also isolated AT2 cells from male F1 mus/cast mice to determine sex-specific gene expression profiling.

(B) Allelic specific reads (RPM) for each expressed X-linked gene which map to the Xa (orange) or Xi (teal). Error bars are standard error of the mean.

(C) Heatmap showing the allele-specific expression for XCI escape genes in AT2 cells. Each replicate sample (1–3) is shown for reads derived from the C57BL/6 or cast allele.

(D) Ace2 is an XCI escape gene in AT2 cells.

(E) Normalized haploid mapped reads from the Xa (orange) and Xi (teal) for four XCI escape genes where there is more expression from the Xi compared with the Xa (Xi > Xa). Error bars are standard error of the mean.

(F) Normalized diploid mapped reads from female (pink) and male (blue) AT2 samples for four XCI escape genes with Xi > Xa. Error bars are standard error of the mean.

(G) Normalized haploid mapped reads from the Xa (orange) and Xi (teal) for the top three XCI escape genes with the highest expression in female AT2 cells. Error bars are standard error of the mean.

(H) Normalized diploid mapped reads from female (pink) and male (blue) samples for the top three XCI escape genes. Statistical significance determined using unpaired t tests for panels B–H (excluding C). Error bars are standard error of the mean.