Project description:Single cell RNA-seq was performed on healthy mouse skin fibroblasts. This data along with single cell transcriptomics datasets of fibroblasts from other healthy tissues was used to construct a steady state mouse fibroblast atlas.
Project description:This study presents a single cell and spatially resolved transcriptomics analysis of human breast cancers. We develop a single cell method of intrinsic subtype classification (scSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using CITE-Seq provides high-resolution immune profiles, including novel PD-L1/PD-L2+ macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell surface protein expression through differentiation within 3 major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into anti-tumor immune regulation. Using single cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer.
Project description:The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While most previous studies have focused on the breast epithelial system, many of the non-epithelial cell types remain understudied. Here, we constructed a comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics data profiled 714,331 cells from 126 women, and 120,024 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data revealed abundant pericyte, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Spatial mapping using four different technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide an unprecedented reference of the adult normal breast tissue for studying mammary biology and diseases such as breast cancer.
Project description:The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While most previous studies have focused on the breast epithelial system, many of the non-epithelial cell types remain understudied. Here, we constructed a comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics data profiled 714,331 cells from 126 women, and 120,024 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data revealed abundant pericyte, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Spatial mapping using four different technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide an unprecedented reference of the adult normal breast tissue for studying mammary biology and diseases such as breast cancer.
Project description:The adult human breast comprises an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue. While most previous studies have focused on the breast epithelial system, many of the non-epithelial cell types remain understudied. Here, we constructed a comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics data profiled 714,331 cells from 126 women, and 120,024 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data revealed abundant pericyte, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. Spatial mapping using four different technologies revealed an unexpectedly rich ecosystem of tissue-resident immune cells, as well as distinct molecular differences between ductal and lobular regions. Collectively, these data provide an unprecedented reference of the adult normal breast tissue for studying mammary biology and diseases such as breast cancer.
Project description:One of the barriers for breast cancer prevention and treatment is our poor understanding of the dynamic cellular shifts that naturally occur within the breast and how these changes contribute to tumour initiation. In this study we report the use of single cell RNA sequencing (scRNAseq) to compile a Human Breast Cell Atlas (HBCA) assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mammoplasties. The data from more than 800,000 cells identified 41 cell subclusters distributed across the epithelial, immune, and stromal compartments. We found that the contribution of these different clusters varied according to the natural history of the tissue. Breast cancer risk modulating factors such as age, parity, and germline mutation affected the homeostatic cellular state of the breast in different ways however, none of the changes observed were restricted to any one cell type. Remarkably, we also found that immune cells from BRCA1/2 carriers had a distinct gene expression signature indicative of potential immune exhaustion which was validated by immunohistochemistry. This suggests that immune escape mechanisms could manifest in non-cancerous tissues during very early stages of tumour initiation. Therefore, the Atlas presented here provides the research community with a rich resource that can be used as a reference for studies on the origins of breast cancer which could inform novel approaches for early detection and prevention.
Project description:The human adrenal glands are highly dynamic endocrine organs that are involved in the secretion of various hormones such as steroids and catecholamines. Here we present a single-nuclei and spatial transcriptomic analysis of healthy adult human adrenal glands to provide a complete adrenal gland atlas. With this, we show how such an atlas can be taken advantage when studying adrenocortical diseases, such as adrenocortical adenomas (ACA). Using nornal adrenal as reference, we showed a high intra-tumoural heterogeneity in the single-nuclei transcriptome of ACA, revealing the presence of specific cell populations associated with cortisol secretion and genetic background.