Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

73 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Human Breast Cell Atlas Mapping the Homeostatic Cellular Shifts in the Adult Breast

ABSTRACT: 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.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER:

PROVIDER: E-MTAB-13664 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): ERP156820

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

The biological and molecular heterogeneity of breast cancers correlate with their cancer stem cell content

Project description:Pathways that govern normal stem cell (SC) function are often subverted in cancer. Here, we report the isolation to near purity of human normal mammary SC (hNMSCs), from cultured mammospheres, based on their ability to retain the lipophilic dye PKH26 as a consequence of their quiescent nature. We demonstrated that PKH26-positive cells possess all the characteristics of hNMSCs. The transcriptional profile of PKH26-positive cells (hNMSC signature) was able to predict biological and molecular features of breast cancers. By using markers of the hNMSC signature, we could prospectively isolate SCs from the normal gland and from breast tumors. Poorly-differentiated aggressive (G3) cancers displayed higher content of prospectively isolated cancer SCs, than well-differentiated less aggressive (G1) cancers. By comparing G3 and G1 tumors in xenotransplantation experiments, we directly demonstrated that G3s are enriched in cancer SCs. Our data support the notion that the heterogeneous phenotypical and molecular traits of human breast cancers are a function of their SC content. Epithelial cells, from reductive mammoplasties, labeled with PKH26 (Sigma, 10-7 M, 5 min) and subjected to FACS analysis using a FACS Vantage SE flow cytometer (Becton&Dickinson) to yield PKH-POS and PKH-NEG cells, were prepared for RNA extraction and hybridization on Affymetrix microarrays. Three independent pools of cells were used, and six Gene Expression Arrays were obtained. No replicates are available.

2009-11-06 | E-GEOD-18931 | biostudies-arrayexpress

Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer

Project description:This SuperSeries is composed of the following subset Series: GSE41194: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 1) GSE41196: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 2) GSE41197: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 3) GSE41198: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 4 stroma) GSE41227: Differentially Expressed Genes Regulating the Progression of Ductal Carcinoma In Situ to Invasive Breast Cancer (Group 4 Epithelial) Refer to individual Series

2012-09-29 | E-GEOD-41228 | biostudies-arrayexpress

Ovarian cancer imputation analysis, LC MS/MS

Project description:Missing values in proteomic data sets have real consequences on downstream data analysis and reproducibility. Although several imputation methods exist to handle missing values, no single imputation method is best suited for a diverse range of data sets, and no clear strategy exists for evaluating imputation methods for large-scale DIA-MS data sets, especially at different levels of protein quantification. To navigate through the different imputation strategies available in the literature, we have established a workflow to assess imputation methods on large-scale label-free DIA-MS data sets. We used three DIA-MS data sets with real missing values to evaluate eight different imputation methods with multiple parameters at different levels of protein quantification; dilution series data set, a small pilot data set, and a larger proteomic data set of clinical ovarian cancer patient samples.

2021-05-07 | PXD023040 | Pride

Pilot data for Imputation, LC-MS/MS

2021-05-07 | PXD022996 | Pride

Single cell profiling of age-dependent and SFB induced transcriptomic changes in small intestinal epithelium and immune system

Project description:In this project, we profiled small intestinal epithelium and lamina propria immune cells from 3-, 4-, 5- and 6-weeks old wild type (WT) littermate animals using 10X droplet based RNA sequencing of single cells. In the second part, we profiled small intestinal epithelium, lamina propria immune cells as well as intraepithelial immune cells from 5-weeks old WT mice derived from Jackson laboratories and littermate colonized with SFB (segmented filamentous bacteria) 2 weeks prior to analysis, using the same approach.

2023-12-31 | E-MTAB-11982 | biostudies-arrayexpress

Single cell profiling of SFB induced transcriptomic changes in small intestinal epithelium and immune system.

Project description:In this project we profiled small intestinal epithelium, lamina propria immune cells as well as intraepithelial immune cells from 5-weeks old WT mice derived from Jackson laboratories and littermate colonized with segmented filamentous bacteria (SFB) 2 weeks prior to analysis, using 10x droplet-based single-cell RNA sequencing.

2023-06-01 | E-MTAB-12391 | biostudies-arrayexpress

IL-33 provision by reprogrammed tumor fibroblastic stromal cells promotes local T cell activity and facilitates melanoma eradication

Project description:The tumor microenvironment (TME) is a complex mixture of tumor cells, immune cells, endothelial cells and fibroblastic stroma cells (FSC). While cancer-associated fibroblasts are generally seen as a tumor-promoting entity, it is conceivable that distinct FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intra-tumoral injection of a recombinant LCMV-based vaccine vector (r3LCMV) expressing the melanocyte differentiation antigen TRP2 results in T cell-dependent eradication of melanomas. Analysis of the TME revealed that viral vector transduction precipitates activation of particular FSC subsets. Using single-cell RNA-seq analysis, we identified a Cxcl13-expressing FSC population with a pronounced immune-stimulatory signature and increased expression of the inflammatory cytokine IL-33. Genetic ablation of Il33 in Cxcl13-Cre+ FSC impeded functionality of intratumoral T cells and consequently tumor control. Thus, reprogramming of distinct FSC subsets in the TME through LCMV-based vectors efficiently promotes tumor eradication by locally sustaining the activity of tumor-specific T cells.

2021-07-03 | E-MTAB-9407 | biostudies-arrayexpress

Affymetrix gene chip analysis for the whole mouse genome transcripts of epithelial and stromal cells from mouse uterine primary co-culture treated with either vehicle or E2

Project description:In the present study, to identify potential paracrine factor for the stromal regulation of E2-induced epithelial cell proliferation, we treated epithelial and stromal cell populations of mouse uterine primary co-culture with either oil or E2. Three independent RNA pools prepared for each population were then subjected to the Affymetrix gene chip analysis for the whole mouse genome transcripts. Our data revealed up-regulation of 119 genes and down-regulation of 28 genes in epithelial cell populations and up-regulation of 144 genes and down-regulation of 192 genes in stromal cell population. We analyzed whole gnenome transcription from epithelial and stromal cell populations of mouse uterine primary co-culture using the Affymetrix GeneChipÂ® Mouse Gene 1.0 ST Array (vehicle vs. E2). 3 replicates were performed.

2013-11-15 | E-GEOD-52399 | biostudies-arrayexpress

A shared transcriptional program in early breast neoplasias despite genetic and clinical distinctions

Project description:The earliest recognizable stages of breast neoplasia are lesions that represent a heterogeneous collection of epithelial proliferations currently classified based on morphology. Their role in the development of breast cancer is not well understood but insight into the critical events at this early stage will improve efforts in breast cancer detection and prevention. These microscopic lesions are technically difficult to study so very little is known about their molecular alterations. To characterize the transcriptional changes of early breast neoplasia, we sequenced 3'- end enriched RNAseq libraries from formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched normal breast and carcinoma samples from 25 patients. We find that gene expression patterns within early neoplasias are distinct from both normal and breast cancer patterns and identify a pattern of pro-oncogenic changes, including elevated transcription of ERBB2, FOXA1, and GATA3 at this early stage. We validate these findings on a second independent gene expression profile data set generated by whole transcriptome sequencing. Measurements of protein expression by immunohistochemistry on an independent set of early neoplasias confirms that ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently upregulated at this early stage. The early neoplasia samples also demonstrate coordinated changes in long non-coding RNA expression and microenvironment stromal gene expression patterns. This study is the first examination of global gene expression in early breast neoplasia, and the genes identified here represent candidate participants in the earliest molecular events in the development of breast cancer. 3SEQ was performed on 72 FFPE human breast samples from 25 patients: 24 normal, 25 early neoplasia, 9 carcinoma in situ, and 14 invasive cancer

2014-05-04 | E-GEOD-47462 | biostudies-arrayexpress

Transcription profiling of normal amplified samples from cancer patients vs. a common reference (part of a set of 5 experiments

Project description:Breast tissue normal. BC-N denotes non-tumor breast tissue samples from breast cancer patients, BC-NRm denotes normal breast tissue samples from reduction mammoplasties.

2007-03-07 | E-SMDB-3961 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data