Publications by authors named "J H Southcombe"

Article Synopsis
  • The Human Endometrial Cell Atlas (HECA) is a comprehensive single-cell reference atlas derived from 313,527 cells, profiling endometrial samples from 63 women, both with and without endometriosis.
  • HECA not only categorizes known cell types but also identifies new ones, utilizing advanced techniques like spatial transcriptomics and validation through an independent single-nuclei dataset.
  • The findings reveal significant cellular interactions in the endometrium, suggest potential dysregulation of specific cell types in endometriosis, and position HECA as a crucial tool for understanding endometrial health and related disorders.
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Background: Endometriosis is a chronic disease affecting 6-10% of women of reproductive age. It is an important cause of infertility and chronic pelvic pain with poorly understood aetiology. CD8+ T (CD8 T) cells were shown to be linked to infertility and chronic pain and play a significant role in lesion clearance in other pathologies, yet their function in endometriosis is unknown.

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Endometriosis is an inflammatory disease that is defined as the growth of endometrium-like tissue outside the uterus, commonly on the lining of the pelvic cavity, visceral organs and in the ovaries. It affects around 190 million women of reproductive age worldwide and is associated with chronic pelvic pain and infertility, which greatly impairs health-related life quality. The symptoms of the disease are variable, this combined with a lack of diagnostic biomarkers and necessity of surgical visualisation to confirm disease, the prognosis can take an average timespan of 6-8 years.

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Study Question: What are the similarities and differences in endometrial B cells in the normal human endometrium and benign reproductive pathologies?

Summary Answer: Endometrial B cells typically constitute <5% of total endometrial CD45 lymphocytes, and no more than 2% of total cells in the normal endometrium, and while their relative abundance and phenotypes vary in benign gynaecological conditions, current evidence is inconsistent.

What Is Known Already: B cells are vitally important in the mucosal immune environment and have been extensively characterized in secondary lymphoid organs and tertiary lymphoid structures (TLSs), with the associated microenvironment germinal centre. However, in the endometrium, B cells are largely overlooked, despite the crucial link between autoimmunity and reproductive pathologies and the fact that B cells are present in normal endometrium and benign female reproductive pathologies, scattered or in the form of lymphoid aggregates (LAs).

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Recurrent Pregnancy Loss (RPL) affects 2-4% of couples, and with increasing numbers of pregnancy losses the risk of miscarrying a euploid pregnancy is increased, suggesting RPL is a pathology distinct from sporadic miscarriage that is due largely to lethal embryonic aneuploidy. There are a number of conditions associated with RPL including unspecified "immune" pathologies; one of the strongest candidates for dysregulation remains T regulatory cells as depletion in the very early stages of pregnancy in mice leads to pregnancy loss. Human endometrial Treg and conventional CD4T cells were isolated during the peri-implantation period of the menstrual cycle in normal women.

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