A Human Breast Cell Atlas Mapping the Homeostatic Cellular Shifts in the Adult Breast
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PROVIDER: PRJEB72028 | ENA |
REPOSITORIES: ENA
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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.
2024-04-03 | E-MTAB-13664 | biostudies-arrayexpress
Project description:Here we use single-cell RNA sequencing to compile a human breast cell atlas assembled from 55 donors that had undergone reduction mammoplasties or risk reduction mastectomies. From more than 800,000 cells we identified 41 cell subclusters across the epithelial, immune and stromal compartments. The contribution of these different clusters varied according to the natural history of the tissue. Age, parity and germline mutations, known to modulate the risk of developing breast cancer, affected the homeostatic cellular state of the breast in different ways. We found that immune cells from BRCA1 or BRCA2 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 very early during tumor initiation. This atlas is a rich resource that can be used to inform novel approaches for early detection and prevention of breast cancer.
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Project description:A human breast transcriptome atlas
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Project description:Single cell atlas of the healthy breast
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Project description:The breast is a dynamic organ whose response to physiological and pathophysiological conditions alters its disease susceptibility, yet the specific effects of these clinical variables on cell state remain poorly annotated. We present a unified, high-resolution breast atlas by integrating single-cell RNA-seq, mass cytometry, and cyclic immunofluorescence, encompassing a myriad of states. We define cell subtypes within the alveolar, hormone-sensing, and basal epithelial lineages, delineating associations of several subtypes with cancer risk factors, including age, parity, and BRCA2 germline mutation. Of particular interest is a subset of alveolar cells termed basal-luminal (BL) cells, which exhibit poor transcriptional lineage fidelity, accumulate with age, and carry a gene signature associated with basal-like breast cancer. We further utilize a medium-depletion approach to identify molecular factors regulating cell-subtype proportion in organoids. Together, these data are a rich resource to elucidate diverse mammary cell states.
2022-05-25 | GSE180878 | GEO
Project description:Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization remains limited. We present 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 macrophage populations with high expression of PD-L1 and PD-L2 immune checkpoint ligands and associations with clinical outcome. We show that mesenchymal cells generate 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.
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Project description:We developed Microwell-seq, a high-throughput and low-cost scRNA-seq platform using simple, inexpensive devices. Using Microwell-seq, we constructed a basic scheme for the Mouse Cell Atlas. We reveal single cell hierarchy for many tissues that have not been well previously characterized. Our study demonstrates the wide applicability of the Microwell-seq technology and the Mouse Cell Atlas resource.
2018-02-14 | GSE108097 | GEO
Project description:Using quantitative proteomics we identified group of synaptic genes with decreased protein synthesis during homeostatic plasticity. To obtain further information about their mRNA levels/sequences (3’UTR) we performed polyA RNAseq. Using EISA analysis of Ribominus RNAseq dataset we could further differentiate between transcriptional respective post-transcriptional dependent alterations in mRNA levels. In addition Ribominus RNAseq from cell body and processes (dendrites, axons) RNA samples showed us local changes in mRNA levels during homeostatic plasticity. At the end, small RNAseq helped us to identify miRNAs that are increased during homeostatic plasticity and might regulate downregulated genes.
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Project description:Cellular Atlas of Human Heart Failure
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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.
2021-06-24 | GSE176078 | GEO