The most comprehensive cell atlas to date of the human uterus has identified two new epithelial cell states that can be used to distinguish two forms of uterine cancer. Researchers from the Wellcome Sanger Institute, the University of Cambridge and their collaborators also identified the genetic pathways that determine two main endometrial cell types.
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The study, published in Nature Genetics, is the first reference map of the uterus to combine single cell and spatial transcriptomics, providing detailed descriptions of cell types as well as where they are situated within the womb lining. Part of the Human Cell Atlas initiative to map every cell type in the human body, the uterine atlas is an important first step towards understanding the endometrium in both health and disease.
The new cell types are found in the endometrium, which is the inner part of the uterus, more commonly known as the womb lining. The top layer of the endometrium sheds and regenerates during a woman’s menstrual cycle, a process regulated by the ovarian hormones oestrogen and progesterone.
One in three women will suffer from some form of reproductive disease during their lifetime. This includes chronic conditions such as endometriosis, as well as potentially life-threatening diseases such as uterine cancers1.
In this study, researchers analysed uterine samples from 15 women of reproductive age using single-cell and spatial transcriptomics. This allowed them to generate a cellular map of the human endometrium that accounted for the dynamic changes during the menstrual cycle.
The team identified two new cell states, known as SOX9+LGR5+ and SOX9+LGR5- , which become more numerous as the epithelium regenerates during the menstrual cycle. They discovered the relative populations of these two cells were connected with two types of endometrial cancer, with tumours carrying a higher proportion of SOX9+LGR5+ associated with more severe disease.
Source: Sanger Institute