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DAC for studying human normal breast cells

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Rene Villadsen
renev@sund.ku.dk

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This DAC controls 3 datasets

Dataset ID	Description	Technology	Samples
EGAD00001008468	The dataset includes 6 FASTQ files with single cell transcriptome sequencing data of normal breast myoepithelial cells from ducts and TDLUs derived from reduction mammoplasties from three patients. Chromium Single Cell 3’ Reagent Kit v2 or v3 (10x Genomics) were used for processing of cells, whereafter sequencing was performed using the Illumina® NextSeq500/550 High Output Kit v2. Cell Ranger was used for generating FASTQ files and files from different lanes were concatenated prior to uploading the data to EGA.	NextSeq 550	6
EGAD50000000723	Basal-like breast cancer originates in luminal progenitors, frequently with an altered PI3K pathway, and focally in close association with genetically altered myoepithelial cells at the site of tumor initiation. The exact trajectory behind this bi-lineage phenomenon remains poorly understood. Here we used a breast cancer relevant transduction protocol including hTERT, shp16, shp53, and PIK3CA(H1047R) to immortalize FACS isolated luminal cells, and we identified a candidate multipotent progenitor. We found that the apparent luminal phenotype of these oncogene transduced progenitors was metastable giving rise to basal-like cells dependent on culture conditions. After culturing the cells for more than 60 passages, cells were subjected to scRNA-seq as well as bulk RNA sequencing of two subpopulations (CD271+ and CD271-).	NextSeq 2000 unspecified	3
EGAD50000002857	Background: We have previously identified a subset of early human breast epithelial progenitors that, despite their luminal affiliation, are enriched for basal markers, including CD146 and keratin 14 (K14). This simultaneous presence of both lineages thus defines a luminal-hybrid state. As luminal progenitors are generally proposed as a cell of origin of breast carcinoma, we examined how cells within this luminal hybrid state relate to breast cancer malignancy. Findings: We first analyzed two patient-derived xenograft (PDX)-derived breast cancer cell lines by dividing cell populations based on CD146-expression by FACS and found that this marker defines a cellular state with increased expression of a selection of luminal hybrid markers, including KRT14. When subjecting the sorted cells to in vitro transwell filter analysis, CD146HI/K14HI luminal hybrid state cells were less invasive. Knocking out either CD146- or K14-expression by CRISPR/Cas9 on a CD146/K14-positive background did not affect the in vivo tumorigenic potential, nor the differentiation state. However, when subjecting the respective sorted populations to a soft agar colony formation assay or as in vivo xenografts, CD146HI/K14HI cells exhibited more growth and metastasis, suggesting that the luminal hybrid state contributes to malignant properties. Conclusions: Our findings demonstrate that multiple components of the luminal hybrid state provide distinct properties to tumor malignancy. The fact that breast cancer can reflect a significant part of the original breast gland differentiation hierarchy may add weight to the argument that the search for novel strategies for treating basal-like breast cancer should include manipulation of cellular differentiation states.	unspecified	12