The endometrium undergoes dynamic changes throughout the menstrual cycle. In a recent study, researchers generated single-cell and spatial reference maps of the human uterus and 3D endometrial organoid cultures.
The human endometrium
The human endometrium (mucosal lining of the uterus) is the site of implantation that provides nutritional support to the placenta during pregnancy. Unlike other mucosal tissue, the endometrium undergoes dynamic, cyclical changes of shedding, regeneration and differentiation. Endometrial dysfunction underpins many common disorders including infertility, miscarriage, pre-eclampsia, endometriosis and endometrial carcinoma. Dissecting the mechanisms that regulate cellular differentiation during the menstrual cycle is important for understanding how normal endometrium are regulated.
Advances in spatial transcriptomics technologies have provided a unique opportunity to resolve tissue architecture as well as underlying cellular interactions. The spatial arrangement of cells is important for understanding morphologically complex tissues such as the endometrium.
Single-cell and spatial transcriptional profiling
In a study, published as preprint in bioRxiv, researchers used single-cell and spatial transcriptional profiling to interrogate the cellular states and spatial of human endometrial cells during the proliferation and secretory phases of the menstrual cycle. The team also profiled 3D endometrial organoids at single-cell resolution to characterise their hormonal responses in vitro. Additionally, they developed a computational toolkit to compare the results with those observed in vivo to benchmark this model system.
From this, the team found common pathways regulating the differentiation for secretory and ciliated lineages in vivo and in vitro. They also showed that in vitro downregulation of WNT or NOTCH signalling pathways increased the differentiation efficiency towards secretory and ciliated lineages, respectively.
This study shows that the combination of genomics, imaging and organoids can create a robust platform for studying endometrial physiology. Most importantly, this map of cellular profiles of the normal endometrium will act as an essential reference for studying many neglected endometrial disorders.
Image credit: By vectorjuice – www.freepik.com