Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

91 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and cancer genome stability.

ABSTRACT: Genomic instability is a prominent driver of tumorigenesis. However, a significant fraction of human cancers display few genomic aberrations, suggesting alternative roads towards malignancy. Here, we show that the differentiation status of normal human mammary epithelial cells influences the early response to an oncogenic activation and determines the genetic routes towards tumorigenesis. Following an oncogenic insult, luminal progenitors and differentiated luminal cells undergo oxidative and DNA replication stress, initiating genomic instability. In contrast, mammary stem cells exhibit the innate capacity to withstand aberrant mitogenic activation, fostering malignant transformation. This property relies upon a pre-emptive program driven by the ZEB1 transcription factor and the methionine sulfoxide reductase MSRB3. The ZEB1-MSRB3 axis governs cellular pliancy and prevents the continuous formation of oncogene-induced DNA damage, leading to neoplasms with unique pathological features. These gene expression data correspond to the different subpopulations that compose the hierarchy of normal human mammary epithelial cells. These subpopulations were freshly isolated from mammary tissue, originating from reduction mammoplasties and flow sorted using four markers (EpCAM, CD10, CD49f, ALDH). Three subpopulations enriched in mammary stem cells (MaSCs) are designed as MaSC1, 2, 3; the luminal progenitor are designed as LP, and the mature luminal cells as mL1 and mL2.

ORGANISM(S): Homo sapiens

SUBMITTER: Arnaud Vigneron

PROVIDER: E-MTAB-4145 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Progesterone and estrogen receptors segregate into different cell subpopulations in the normal human breast

Project description:Gene expression profiles of normal human mammary epithelial cell subsets enriched for luminal or myoepithelial characteristics on the basis of EpCAM and CD49f expression. Transcription profiles were compared between luminal- and myoepithelial-enriched human MEC subsets following 3D culture from 4 individuals. Gene expression profiles of normal human mammary epithelial cell subsets enriched for mature, luminal progenitor or bipotent progenitor-enriched characteristics on the bais of CD49f, MUC1, CD10, CD133 and Thy1 expression Transcription profiles were compared between unsorted, mature, luminal progenitor-enriched and bipotent progenitor-enriched human MEC subsets following 3D culture from 2 individuals. Four replicates of luminal-enriched human MECs and 3 replicates of myoepithelial-enriched MECs Transcription profiles of two replicates of unsorted, mature, luminal progenitor-enriched and bipotent progenitor-enriched human MEC subsets were analysed following 3D culture

2012-08-17 | E-GEOD-31429 | biostudies-arrayexpress

Expression data from mouse luminal mammary epithelial cells

Project description:We used a mouse strain in which one Tbx3 gene was replaced with the yellow fluorescent protein variant Venus. Luminal cells had either very high Tbx3 promoter activity or not at all. We performed an expression analysis on luminal mammary epithelial cells sorted based on their Venus expression (reporting Tbx3 promoter activity) to investigate the difference between these two cell populations. Mammary epithelial cells from 3 Tbx3-Venus-KI adult virgin female mice (FVB background) were pooled and luminal cells were sorted into a Venus-hi and a Venus-neg sample. There were no repeats for this study.

2014-08-20 | E-GEOD-58327 | biostudies-arrayexpress

ATAC-seq of mouse luminal progenitors isolated from wild-type or Blg-Cre;Brca1f/f;p53+/- mouse models

Project description:One of the major hurdles for the early detection of cancer is our poor understanding of tumour initiating events. Historically, cancer research has focused on histological and molecular characterisation of established tumours which has led to the identification of hundreds of putative driver mutations. It is currently unclear how these genetic aberrations impact the cell state of nascent tumour cells and their microenvironment. BRCA1 driven triple negative breast cancer (TNBC) for example has been shown to arise from luminal progenitor cells yet little is known about how BRCA1 loss-of-function (LOF) and concomitant mutations affect the luminal progenitor cell state. This repository contains ATAC-sequencing dataset of luminal progenitors isolated from 6-months old Brca1/p53 and wild-type mice. This data was used to show that the perturbation of Brca1/p53in luminal progenitors induces an aberrant alveolar differentiation pre-malignancy. Unlike alveolar differentiation occurring during gestation, this process is cell autonomous and characterised by the dysregulation of transcription factors driving alveologenesis. The ATAC-sequencing data supports a model where transcriptional and epigenetic changes driven by Brca1/p53 inadvertently promote a differentiation program hardwired in luminal progenitors, highlighting the deterministic role of the cell of origin and offering a potential explanation for the tissue specificity of BRCA1 tumours.

2021-02-02 | E-MTAB-10054 | biostudies-arrayexpress

Mouse mammary epithelial cell subpopulations from pregnant and virgin mice

Project description:To study the effect of pregnancy on mouse mammary epithelial subpopulations, epthelial cells derived from virgin or pregnant (12.5 day pregnant) mice were isolated using fluorescence-activated cell sorting. After elimination of haematopoietic and endothelial cells, two distinct epithelial subpopulations were sorted using antibodies against CD29 and CD24. Based on the immunohistochemical phenotype, and in vivo and in vitro functional assays, these subpopulations were identified as mammary stem cell enriched (CD29hiCD24+) and luminal (CD29loCD24+) respectively (ref: Shackleton et al, Nature 2006). Microarray profiling was used to compare gene expression profiles of the two subpopulations in 12.5 day pregnant and virgin mice. For each biological replicate, mammary gland from virgin or 12.5 day pregnant FVB/NJ mice were collected and digested to obtain a single cell suspension. CD45-CD31-TER119- cells were then sorted based on the expression of cell surface markers CD24 and CD29. There were 4 pools of pregant mice and 3 pools of virgin mice.

2010-04-10 | E-GEOD-20402 | biostudies-arrayexpress

Mammary epithelial cell subpopulations from control and ovariectomized mice

Project description:To study the effect of pregnancy on mouse mammary epithelial subpopulations, epthelial cells derived from control or ovariectomized adult mice were isolated using fluorescence-activated cell sorting. After elimination of haematopoietic and endothelial cells, two distinct epithelial subpopulations were sorted using antibodies against CD29 and CD24. Based on the immunohistochemical phenotype, and in vivo and in vitro functional assays, these subpopulations were identified as mammary stem cell enriched (CD29hiCD24+) and luminal (CD29loCD24+) respectively (ref: Shackleton et al, Nature 2006). Microarray profiling was used to compare gene expression profiles of the two subpopulations isolated from ovariectomized and control mice. For each of two biological replicates, 6 FVB/NJ mice were ovariectomized at 8 weeks of age. 4 weeks after ovariectomy (Ovx) mammary gland from control or Ovx animals were collected and digested to obtain a single cell suspension. CD45-CD31-TER119- cells were then sorted based on the expression of cell surface markers CD24 and CD29. Similarly for two pools of control mice. There were also 4 technical replicates, to make 12 BeadChips in total.

2010-04-10 | E-GEOD-20401 | biostudies-arrayexpress

Developmental changes in the in vitro activated regenerative activity of primitive mammary epithelial cells

Project description:Many normal adult tissues contain rare stem cells with extensive self-maintaining regenerative potential. During development, the stem cells of the hematopoietic and neural systems undergo intrinsically specified changes in their self-renewal potential. In the mouse, mammary stem cells with transplantable regenerative activity are first detectable a few days before birth. They share some phenotypic properties with their adult counterparts but are enriched in a subpopulation that displays a distinct gene expression profile. Here we show that fetal mammary epithelial cells have a greater direct and inducible growth potential than their adult counterparts. The latter feature is revealed in a novel culture system that enables large numbers of mammary stem cells with serially transplantable activity as well as in vitro clonogenic progenitors to be produced within 7 days from single fetal or adult input cells. We further show that these responses are highly dependent on novel factors produced by fibroblasts. These findings provide new avenues for elucidating mechanisms that regulate normal mammary epithelial stem cell properties at the single-cell level, how these change during development, and how their perturbation may contribute to transformation. We used microarrays to compare the transcriptome of E18.5 fetal and adult MRU-enriched mammary cells. Three biological replicates each of CD31-CD45-Ter119-BP-1-EpCAM+CD49f+ adult basal cells and CD31-CD45-Ter119-EpCAM++CD49f+ fetal cells were sorted. RNA was extracted and hybridized to the Agilent One-Color Gene Expression Arrays .

2013-08-13 | E-GEOD-46357 | biostudies-arrayexpress

A Basal Stem Cell Signature Identifies Aggressive Prostate Cancer Phenotypes

Project description:Aggressive cancers and normal stem cells often share similar molecular and functional traits. It is unclear if aggressive phenotypes of prostate cancer molecularly resemble normal stem cells residing within the human prostate. We performed high-throughput RNA sequencing on uncultured, highly purified epithelial populations from human prostates obtained after radical prostatectomy. We found the basal population to be defined by genes associated with developmental programs, epigenetic remodeling, and invasiveness. We further generated a 91-gene basal signature and applied it to gene expression datasets from patients with organ-confined or castration-resistant, metastatic prostate cancer. Metastatic prostate cancer was more enriched for the basal stem cell signature than organ-confined prostate cancer. Moreover, histological subtypes within prostate cancer metastases varied in their enrichment of the stem cell signature with small cell neuroendocrine carcinoma being the most stem cell-like. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common to all three signatures. These results suggest that the most aggressive variants of prostate cancer share a core transcriptional program with normal prostate basal stem cells. Transcriptional analysis of 10 uncultured prostatic basal and luminal populations from either the benign or malignant prostate tissue of 8 human prostate cancer patients by high-throughput RNA-seq

2016-06-01 | E-GEOD-82071 | biostudies-arrayexpress

Microarray expression profiling study of Runx1-null and wild type luminal mammary epithelial cells

Project description:RUNX1 encodes a RUNX family transcription factor (TF) and was recently identified as a novel mutated gene in human luminal breast cancers. We found that Runx1 is expressed in all subpopulations of murine mammary epithelial cells (MECs) except the secretory alveolar luminal cells. Conditional knockout of Runx1 in MECs by MMTV-Cre led to a decrease in luminal MECs, largely due to a profound reduction in the estrogen receptor (ER)-positive mature luminal subpopulation, a phenotype that could be rescued by loss of either Trp53 or Rb1. Mechanistically RUNX1 represses Elf5, a master regulatory TF gene for alveolar cells, and activates Foxa1, a key mature luminal TF gene involved in the ER program. Collectively, our data identified a key regulator of the ER+ luminal lineage whose disruption may contribute to development of ER+ luminal breast cancer when under the background of either TP53 or RB1 loss. Thoracic and inguinal mammary glands from 3 MMTV-Cre;Runx1L/L;R26Y and 3 MMTV-Cre;Runx1+/+;R26Y adult virgin females were dissected out, minced and digested to single cell suspension. Runx1L is the floxed conditional knockout allele of Runx1. R26Y is a conditional YFP reporter that would be turned on upon Cre-mediated recombination. FACSaria machine was used to sort out the YFP-marked luminal epithelial cell population of each of these 6 mice. Total RNA was isolated with Qiagen RNeasy kit and subsequently amplified by Nugen V2 and applied to Affymetrix mouse genome 430 2.0 arrays.

2014-11-26 | E-GEOD-47375 | biostudies-arrayexpress

Gene expression profiles of normal mouse mammary cell subpopulations FACS sorted based on expression of biomarkers

Project description:To delineate epithelial subpopulations in mouse mammary tissue, hematopoietic and endothelial cells were depleted from freshly isolated cell suspensions derived from mammary glands using fluorescence-activated cell sorting. The resultant Lin- population was fractionated into four distinct subpopulations using antibodies against CD29, CD24 and CD61. Based on the immunohistochemical phenotype, and in vivo and in vitro functional assays, these subpopulations were identified as fibroblast-containing stromal (CD29loCD24-), mammary stem cell (MaSC)-enriched (CD29hiCD24+CD61+), luminal progenitor (CD29loCD24+CD61+), and mature luminal (CD29loCD24+CD61-) cell subpopulations. Microarray profiling was used to derive gene expression signatures of these 4 subpopulations. The four mammary cell subpopulations were found to have distinct gene expression profiles. Four mammary cell subpopulations from 3-5 pooled mouse tissues were analysed. MS is for the MaSC-enriched cell subpopulation. LP is for the Luminal Progenitor subpopulation. ML is for the Mature Luminal subpopulation.

2010-03-20 | E-GEOD-19446 | biostudies-arrayexpress

Control of mammary stem cell function by steroid hormone signalling.

Project description:This SuperSeries is composed of the following subset Series: GSE20401: Mammary epithelial cell subpopulations from control and ovariectomized mice GSE20402: Mouse mammary epithelial cell subpopulations from pregnant and virgin mice Refer to individual Series

2010-07-08 | E-GEOD-22446 | 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