ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/090/SRR19241990/SRR19241990_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/092/SRR19241992/SRR19241992_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/089/SRR19241989/SRR19241989_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/088/SRR19241988/SRR19241988_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/087/SRR19241987/SRR19241987_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/090/SRR19241990/SRR19241990_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/091/SRR19241991/SRR19241991_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/085/SRR19241985/SRR19241985_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/087/SRR19241987/SRR19241987_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/092/SRR19241992/SRR19241992_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/086/SRR19241986/SRR19241986_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/091/SRR19241991/SRR19241991_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/089/SRR19241989/SRR19241989_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/088/SRR19241988/SRR19241988_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/086/SRR19241986/SRR19241986_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR192/085/SRR19241985/SRR19241985_1.fastq.gzprimaryOK200GenomicsUniversity of Pennsylvaniahttps://www.ebi.ac.uk/ena/browser/view/PRJNA838948Mus musculusSignificant sex differences exist for many lung pathologies, including SARS-CoV-2 related disease (COVID-19) and pulmonary fibrosis, but the mechanistic basis for this remains unclear. Notably, Ace2, the gene encoding angiotensin-converting enzyme 2, an enzyme that plays multiple roles in SARS-CoV-2 pathogenesis, including acting as the major viral receptor, is localized on the X-chromosome. Moreover, prior work in fibroblasts suggested that Ace2 may escape X-Chromosome Inactivation (XCI), which normalizes X-lined gene expression between sexes. Alveolar type 2 cells (AT2s), which play a key role in alveolar lung regeneration, express Ace2, suggesting that aberrant XCI in AT2s could potentially impact sex-biased lung pathology. To that end, we performed RNA-seq on AT2 cells isolated from 4 male and 4 female F1 mus/cast mice. Utilizing allele-specific transcriptomics, we demonstrate that about 50% of expressed X-linked genes in mouse AT2s, including Ace2, escape XCI, the highest levels reported to date. Moreover, we observe dramatic genome-wide expression differences between male and female AT2s, likely influencing both lung physiology and pathophysiologic responses. Taken together, these studies support a renewed focus on AT2s as potential contributor to sex-biased differences in lung disease. Overall design: Comparative gene expression profiling analysis of RNA-seq data for Alveolar Type 2 (AT2) cells from 4 male and 4 female F1 mus/cast mice.xref:PubMed:36638790ENAGenotypic, Sex, sex, Genotypic Sex, Spi9, Phenotypic Sex, Angiotensin II type-2 receptor, ATII, ATGR2, MRX88, Cell., TII, ovalbumin, lung type II cell, Phenotypic, at2, at2r, AT2Genotypic, Sex, sex, Genotypic Sex, Spi9, Phenotypic Sex, Angiotensin II type-2 receptor, ATII, ATGR2, MRX88, Cell., TII, ovalbumin, lung type II cell, Phenotypic, at2, at2r, AT2falseXCI and sex-biased expression in AT2 cellsXCI and sex-biased expression in AT2 cells2025-09-242023-01-27PRJNA838948GSE2031661009036638790