Cellular indexing of transcriptomes and epitopes by sequencing unveils coordinated RNA and protein landscape in ovary at single-cell resolution

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Polycystic ovary syndrome (PCOS), a prevalent multisystem endocrine disorder affecting women of reproductive age, is characterized by intertwined reproductive-metabolic axis dysfunction encompassing ovarian impairment, insulin resistance, and systemic metabolic dysregulation. Nevertheless, the intricate pathophysiology, especially regarding the coordinated RNA/protein targets among distinct ovarian cellular populations, remains inadequately elucidated at the single-cell level. Herein, we have developed a single-cell transcriptomic atlas of human ovaries, highlighting the dysregulation of LUM and SOD3 in mesenchymal and epithelial compartments in PCOS. By utilizing Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) technology, we have concurrently characterized transcriptomes and 163 antibody-derived tags (ADTs) in human ovarian cells, establishing the inaugural multi-omic atlas of PCOS ovaries derived from single-cell transcriptomes and cell-surface proteomes. Our analysis has revealed a strong correlation between RNA and protein expression levels across major ovarian cellular populations. Particularly, CD86 and CD14 displayed significant upregulation in PCOS epithelial cells, with functional enrichment suggesting the regulation of PCOS through cytokine-cytokine receptor interactions and cell adhesion signatures. Through a methodical analysis of concordant differentially expressed protein-RNA pairs, we have ascertained that HLA-DRA was upregulated in PCOS. These discoveries lay the groundwork for integrating single-cell transcriptomics with protein profiling to elucidate previously unexplored facets of coordinated protein-RNA pairs for PCOS.

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