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The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma. Single-cell and spatial transcriptomic profiling of the human endometrium highlights pathways governing the proliferative and secretory phases of the menstrual cycle. Analyses of endometrial organoids show that WNT and NOTCH signaling modulate differentiation into the secretory and ciliated epithelial lineages, respectively. Correction in: Nature Genetics, 55, page 165 (2023)DOI: 10.1038/s41588-022-01287-6

Nanodiamonds have demonstrated potential as powerful sensors in biomedicine, however, their translation into routine use requires a comprehensive understanding of their effect on the biological system being interrogated. Under normal fabrication processes, nanodiamonds are produced with a graphitic carbon shell, but are often oxidized in order to modify their surface chemistry for targeting to specific cellular compartments. Here, we assessed the biological impact of this purification process, considering cellular proliferation, uptake, and oxidative stress for graphitic and oxidized nanodiamond surfaces. We show for the first time that oxidized nanodiamonds possess improved biocompatibility compared to graphitic nanodiamonds in breast cancer cell lines, with graphitic nanodiamonds inducing higher levels of oxidative stress despite lower uptake. ispartof: NANOSCALE vol:10 issue:25 pages:12169-12179 ispartof: location:England status: published