In a paper published in Nature Genetics, researchers at Cedars-Sinai Medical Center have revealed the most detailed molecular profile to date of endometriosis. The hope is that this could aid the development of therapeutic treatments for this debilitating disease.
End in sight for endometriosis?
Endometriosis affects around 1 in 10 women and is characterised by headaches, fatigue, chronic pain, bowel and bladder dysfunction, and infertility. It can affect women from puberty to menopause and is caused by cells of the uterine lining (or endometrial tissue) growing in places they shouldn’t – like the ovaries, fallopian tubes and abdominal cavity. It also often associated with an elevated risk of ovarian cancer.
Currently, there is no cure for endometriosis, and treatment options are aimed at reducing symptoms – from pain relief and hormonal treatments to more drastic measures such as surgery to remove cysts or even a hysterectomy.
“Endometriosis has been an understudied disease, in part because of limited cellular data that has hindered the development of effective treatments,” said Kate Lawrenson, an associate professor in the Department of Obstetrics and Gynecology at Cedars-Sinai, and co-senior author of the study. To combat this lack of data, Lawrenson and her team turned to single-cell analysis.
Profiling single cells
“In this study we applied a new technology called single-cell genomics, which allowed us to profile the many different cell types contributing to the disease,” said Lawrenson.
Using samples from just 21 patients, the team managed to analyse more than 370,000 individual cells, creating an improved cellular database of the disease. They profiled the transcriptomes of individual cells from endometriomas, endometriosis, eutopic endometrium, unaffected ovary and endometriosis-free peritoneum. “We were able to identify the molecular differences between the major subtypes of endometriosis, including peritoneal disease and ovarian endometrioma,” added Lawrenson.
The authors noted that the molecular signatures of endometrial-type epithelium and stroma differed across tissue types, suggesting a role for cellular restructuring and transcriptional reprogramming in the disease. Other findings included the dysregulation of pro-inflammatory pathways, upregulation of complement proteins, and a mutation that led to enrichment of lymphatic endothelial cells.
The hope is that by creating this detailed map of endometriosis, it can aid the development of better treatments in the future. “Identifying these cellular differences at such a detailed level should allow us to better understand the origins, natural progression, and potential therapeutic targets for treatment. We are currently limited to hormonal therapy and surgical excision, with variable success and frequent recurrence of disease,” said Matthew Siedhoff, vice chair of Gynecology at Cedars-Sinai and a co-author of the study.
It turns out there’s also a link between endometriosis and cancer – many women with endometriosis have a slightly higher risk of developing cancer in their lifetime, and scientists have for many years noticed the similarities between the two diseases.
“[Endometriosis] can travel throughout the body, so in many ways it behaves like cancer. But why does endometriosis behave like cancer while rarely becoming cancer? Large-scale next generation sequencing projects have been incredibly helpful in understanding how cancer works and in designing targeted therapeutics. We expect it can do the same for endometriosis,” said Lawrenson.
The next step for the Cedars-Sinai researchers is to use the cellular atlas to test therapeutic targets in a mouse model. “This resource can now be used by researchers all throughout the world to study specific cell types that they specialize in, which will hopefully lead to more efficient and effective diagnosis and treatment for endometriosis patients. It really is a game changer,” said Lawrenson.