Abstract: Endometrial lesions are highly complex tissues comprised of cells of endometrial, immune and vascular origin. An interplay among these cell types and factors in the local environment is key to the establishment, progression and spread of these lesions. An unbiased single cell transcriptomic approach to comprehensively identify all the cellular components of ectopic lesions and their microenvironment is essential for understanding the environmental etiology and pathophysiology of endometriosis. We generated single cell transcriptomic (scRNAseq) data from peritoneal and ovarian endometriosis lesions from stage III-IV endometriosis patients, using a droplet-based RNAseq platform. Matched eutopic endometrium were also analyzed by scRNAseq.

Our unbiased single cell approach allows us to capture multiple cell types from both ectopic and eutopic endometrium. We identified the major cell types composing the ectopic endometrium as well its microenvironment in the adjacent peritoneum. Cell types identified within the microenvironment included T cells, B cells, macrophages, endothelial, fibroblast, muscle cells and pericytes. Notably, we were able to identify several subtypes of myeloid cells and their differential gene expression analysis revealed substantial differences revealing their role in angiogenesis and immunosuppression. We identified a lesion-specific pericyte subtype, implicated in immune cell trafficking. Image Mass Cytometry analysis of the lesions revealed important clues on the spatial organization and the cellular interplays withing cell types that were characterized transcriptionally.

Our approach allows to study the diversity of cells composing the endometriosis lesions and their microenvironment, and to compare ectopic lesions to eutopic endometrium. Together, the unbiased study of endometriosis and its microenvironment at the single cell level offers a powerful insight into the key cellular players of endometriosis.

Biography: My research career began in Spain where I worked on human-based stem cell therapies for Parkinson’s disease during my PhD. I expanded my stem cell training as a postdoctoral fellow by joining a team working at the intersection of tumor biology and mouse genetics, with a particular focus on lung and colorectal cancers during my postdoc at the Institute for Molecular Biology, A-STAR in Singapore. Later I joined the Robson lab at the Genome Institute of Singapore, A-STAR, where I continued to study the biology of lung and colorectal tumors, using and generating novel single-cell profiling technologies.

In my current role as an Associate Director for the Single Cell Biology Lab at The Jackson Laboratory for Genomic Medicine (JAX-JGM, USA), I continue to investigate the cellular heterogeneity of human tissues using state-of-the-art single-cell ‘omics’ approaches, 3D- cell culture models and high content screening systems.