Oszlanczi, A. | bioRxiv Science

bioRxiv2023

An integrated single-cell reference atlas of the human endometrium

The human endometrium, the inner lining of the uterus, exhibits complex, dynamic changes throughout the menstrual cycle in response to ovarian hormones. Aberrant response of endometrial cells to hormones is associated with multiple disorders, including endometriosis. Previous single-cell studies of the endometrium profiled a limited number of donors and lacked consensus in defining cell types and states. Here, we introduce the Human Endometrial Cell Atlas (HECA), a high-resolution single-cell reference atlas, combining published and newly generated single-cell transcriptomics datasets of endometrial biopsies of women with and without endometriosis. The HECA assigned consensus cell types and states, and uncovered novel ones, which we mapped in situ using spatial transcriptomics. We quantified how coordinated interactions between cell states in space and time contribute to endometrial regeneration and differentiation. In the continuously changing functionalis layer, we identified an intricate coordination of TGF{beta} signalling between stromal and epithelial cells, likely crucial for cell differentiation. In the basalis layer, we defined signalling between fibroblasts and a new epithelial cell population expressing epithelial stem/progenitor markers, suggesting their role in endometrial regeneration. Additionally, integrating the HECA single-cell data with genome-wide association study data and comparing endometrial samples from women with and without endometriosis, we pinpointed subsets of decidualised stromal cells and macrophages as the most dysregulated cell states in endometriosis. Overall, the HECA is an invaluable resource for studying endometrial physiology, investigating endometrial disorders, and guiding the creation of endometrial microphysiological in vitro systems.

genomics↗

bioRxiv2021

A spatial multi-omics atlas of the human lung reveals a novel immune cell survival niche

Multiple distinct cell types of the human lung and airways have been defined by single cell RNA sequencing (scRNAseq). Here we present a multi-omics spatial lung atlas to define novel cell types which we map back into the macro- and micro-anatomical tissue context to define functional tissue microenvironments. Firstly, we have generated single cell and nuclei RNA sequencing, VDJ-sequencing and Visium Spatial Transcriptomics data sets from 5 different locations of the human lung and airways. Secondly, we define additional cell types/states, as well as spatially map novel and known human airway cell types, such as adult lung chondrocytes, submucosal gland (SMG) duct cells, distinct pericyte and smooth muscle subtypes, immune-recruiting fibroblasts, peribronchial and perichondrial fibroblasts, peripheral nerve associated fibroblasts and Schwann cells. Finally, we define a survival niche for IgA-secreting plasma cells at the SMG, comprising the newly defined epithelial SMG-Duct cells, and B and T lineage immune cells. Using our transcriptomic data for cell-cell interaction analysis, we propose a signalling circuit that establishes and supports this niche. Overall, we provide a transcriptional and spatial lung atlas with multiple novel cell types that allows for the study of specific tissue microenvironments such as the newly defined gland-associated lymphoid niche (GALN).

cell biology↗