Human Endometrial Cell Atlas published

Researchers have developed a comprehensive cell map of the human endometrium, and identified new cell types and interactions between them.

The human endometrium plays a vital role in human reproduction by supporting pregnancy when an embryo implants. If implantation does not happen, the tissue sheds and regenerates each month without scarring. Previous studies have failed to characterise the endometrium at different phases of the menstrual cycle and therefore not reached a consensus on the cells that exist in the endometrium. The new Human Endometrial Cell Atlas from Wellcome Sanger Institute researchers now includes data from around 626,000 cells across 121 people, containing both those with and without endometriosis, during natural menstrual cycles and while using hormonal contraception.

'Having this in-depth and large-scale genomic resource on the endometrium is invaluable if we are ever going to fully understand how the endometrium functions in health and what goes wrong in conditions such as endometriosis. Developing a non-invasive diagnostic test and effective treatment for this debilitating condition has been a priority for clinicians, researchers and those with endometriosis worldwide,' said Magda Marečková, co-first author from the Nuffield Department of Women's and Reproductive Health, University of Oxford and Wellcome Sanger Institute.

Endometriosis is a chronic condition characterised by endometrium-like tissue that appears outside the uterus. Accompanied with severe pain and fertility problems, it is the second most common gynaecological condition in the UK. However, there is currently no cure for it and the cause of the condition remains unknown.

Published in Nature Genetics, this project is part of the larger Human Cell Atlas project, which aims to map all cell types in the body to enhance our understanding of health and disease. The scientists discovered several new cell types that appear only during specific phases of the menstrual cycle and investigated the interactions between immune cells, known as macrophages, stromal cells (a type of connective tissue cell) and blood vessels, which play a role in the endometrium's scarless regeneration.

Combining their detailed cellular map of the endometrium with data from a large genome-wide association study published in 2023 (see BioNews 1183), the team highlighted four cell types, including two types of immune cells and two types of stromal cells, that are likely affected by genetic changes linked to endometriosis. They also found particular signalling pathways were dysregulated in those with endometriosis.

'While further research and validation is needed, our study suggests that certain cells and pathways are dysregulated in endometriosis and if replicated in additional studies, they could be potential diagnostic and therapy targets in the future,' Marečková said.

The authors suggest that these cell types and signalling pathways could play a role in endometriosis and could offer new avenues for future research into how genetic changes contribute to the condition.