Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell dissection of Comma-1D cultures reveals cell populations with unique differentiation and transformation properties [bulk RNA-Seq]

ABSTRACT: The mammary epithelial tree is a heterogeneous structure that contains two main populations, luminal and basal, with distinct molecular and functional characteristics. The investigation of how this heterogeneity is developed and how it influences breast tumorigenesis has been hampered by the need to perform these studies using animal models due to the lack of relevant, tractable, and fully characterized in vitro models. Comma-1D is an immortalized mouse mammary epithelial cell line that has unique morphogenetic properties particularly its ability to generate cells of luminal and basal lineages. Here, we perform single-cell RNA-seq studies to dissect its heterogeneous nature. Our analysis reveals that Comma-1D cultures consist of two main populations with luminal and basal features and a smaller population with mixed lineage and bipotent characteristics. Additionally, we demonstrate that multiple transcription factors associated with the differentiation of the mammary epithelium in vivo also modulate this process in Comma-1D cultures. Finally, we have used the Comma-1D model to study how the cellular subtype of origin influences the response to cancer-promoting mutations. We found that only cells with luminal molecular features were able to acquire transformed characteristics after an oncogenic HER2 mutant was introduced in their genomes. Overall, the studies present here characterize at a single-cell level the heterogeneity of the Comma-1D cell line and illustrate how the unique properties of Comma-1D cells can be used as an experimental model to study both the differentiation and the transformation processes in vitro.

ORGANISM(S): Mus musculus

PROVIDER: GSE182351 | GEO | 2022/05/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Single-cell dissection of Comma-1D cultures reveals cell populations with unique differentiation and transformation properties [scRNA-Seq]

Project description:The mammary epithelial tree is a heterogeneous structure that contains two main populations, luminal and basal, with distinct molecular and functional characteristics. The investigation of how this heterogeneity is developed and how it influences breast tumorigenesis has been hampered by the need to perform these studies using animal models due to the lack of relevant, tractable, and fully characterized in vitro models. Comma-1D is an immortalized mouse mammary epithelial cell line that has unique morphogenetic properties particularly its ability to generate cells of luminal and basal lineages. Here, we perform single-cell RNA-seq studies to dissect its heterogeneous nature. Our analysis reveals that Comma-1D cultures consist of two main populations with luminal and basal features and a smaller population with mixed lineage and bipotent characteristics. Additionally, we demonstrate that multiple transcription factors associated with the differentiation of the mammary epithelium in vivo also modulate this process in Comma-1D cultures. Finally, we have used the Comma-1D model to study how the cellular subtype of origin influences the response to cancer-promoting mutations. We found that only cells with luminal molecular features were able to acquire transformed characteristics after an oncogenic HER2 mutant was introduced in their genomes. Overall, the studies present here characterize at a single-cell level the heterogeneity of the Comma-1D cell line and illustrate how the unique properties of Comma-1D cells can be used as an experimental model to study both the differentiation and the transformation processes in vitro.

2022-05-04 | GSE182352 | GEO

Leveraging single cell transcriptomics and custom high throughput functional screening assays to resolve cell type, growth kinetic, and stemness heterogeneity within Comma-1D

Project description:We investigated the heterogeneous cell populations within the Comma-1D cell line through single cell RNA sequencing technologies. The assay sequenced over 5,000 cells composing 8 unique subclusters. Populations detected included luminal, myoepithelial, and fibroblast like cell types.

2021-12-31 | GSE182589 | GEO

Cyclin D1, Id2 and Sox9 are upregulated in a lobular competent COMMA Db clonal derivative’ cells compared to a lobular incompetent clone both in vitro, and in vivo

Project description:Understanding underlying mechanisms responsible for the differentiation and stemness of mouse mammary progenitor cells are paramount to understanding the heterogeneity of mammary development and tumorigenesis. Consequently, studies have isolated and characterized mouse mammary progenitor cell lines such as: COMMA-1D, NSP2 and SP3, but have not parsed the various transcriptomes that play a role in progenitor differentiation and mammary gland development.

2018-10-19 | GSE121499 | GEO

RNA-seq of ID4 knockdown Comma-Dβ mammary epithelial cells

Project description:The goal of this study was to determine the genes regulated by ID4 in mammary epithelial cells. ID4 was knocked down by siRNA in the mammary epithelial cell line Comma-Dβ and RNA-seq was performed following 48 hr to determine differentially expressed genes.

2020-05-07 | GSE149966 | GEO

HEB and histone mark ChIP-seq in Comma-Dβ mouse mammary epithelial cells

Project description:The goal of this study was to determine the genome wide binding sites of the E-protein transcription factor HEB in mammary epithelial cells, and to delineate the chromatin context of these regions. ChIP-seq for HEB, H3K4Me3, H3K27Ac, and H3K27Me was performed in Comma-Dβ cells in quadruplicate.

2020-05-07 | GSE149967 | GEO

Hesperia comma

Project description:Hesperia comma overview

| PRJNA724778 | ENA

The histone demethylase KDM6A controls the mammary luminal lineage through enzyme-independent mechanisms

Project description:Mammary ducts and alveoli are composed of basal and luminal cells, with the fate and differentiation of secreting cells being controlled by hormones through specific transcription factors. This study establishes the essential role of the histone H3 lysine 27 trimethylation (H3K27me3) demethylase KDM6A (UTX) in a balanced basal and luminal cell compartment. Disproportionate formation of basal cells in the absence of KDM6A resulted in disorganized mammary ducts and alveoli and lactation failure. Mutant luminal progenitors lost their distinctive transcription factor expression pattern and acquired basal characteristics leading to a preferential expansion of this lineage. The structure of mammospheres obtained from mutant progenitors suggested they were derived from basal progenitors. The genomic H3K27me3 landscape was unaltered in the absence of KDM6A suggesting demethylase-independent mechanisms. In support of this, mammary tissue developed normally in mice expressing a catalytically inactive KDM6A. This study demonstrated that mammary luminal progenitor cells rely on UTX to stably maintain their identity and thereby establish a balance of basal and luminal cells required for a functional mammary gland.

2016-06-06 | GSE77586 | GEO

Lineage plasticity enables low-ER luminal tumors to evolve and gain basal-like traits

Project description:Breast tumors expressing lower levels of Estrogen Receptor (ER) represent a distinct subset of breast cancer characterized by the emergence of basal-like characteristics within tumors that are traditionally considered luminal-like. Lineage tracing of these low-ER tumors in the MMTV-PyMT mouse mammary tumor model revealed that the basal-like tumor cells within these tumors arose from normal luminal epithelial cells, suggesting that luminal-to-basal plasticity is responsible for the evolution and emergence of basal-like characteristics within these tumors. This study aims to identify the potential drivers of this plasticity by using single-cell RNA sequencing to identify populations of lineage-restricted luminal cells and luminal-derived basal cells within the tumor, and comparing their gene expression profiles.

2023-03-01 | GSE214815 | GEO

Affymetrix SNP array data for Trp53-null mammary tumors developed in a mouse model with a K8+ luminal cell origin

Project description:Mammary epithelium is hierarchically organized, with multipotent basal mammary stem cells (MaSCs) producing both luminal and basal cells during development or upon transplantation. Recent studies suggested that most breast cancers, including Basal-Like breast cancer (BLBC), might originate from luminal cells, and oncogenic events, such as ectopic expression of PIK3CA(H1047R), could induce multipotency in committed luminal cells. p53 is the most commonly mutated gene in human breast cancer; in particular, its inactivating mutations are found in most BLBCs, raising a question as to whether p53-loss plays a key role in acquisition of multipotent MaSC-like properties by luminal cells. By in situ lineage-tracing, we found that induced loss of p53 in Keratin 8 (K8)+ luminal cells led to their clonal expansion, due to increased cell cycle activity and attenuated apoptosis control, but did not directly affect their luminal identity. All induced mice eventually developed either Claudin-Low mammary tumors with 9qA1 (Yap1) amplification or Basal-Like tumors with 6qA1-A2 (Met) amplification. These data suggest that although p53 does not directly control the luminal fate, its loss facilitates acquisition of MaSC-like properties by luminal cells and predisposes them to development of mammary tumors with loss of luminal identity.

2016-12-20 | GSE77497 | GEO

Gene expression profiles from mammary tissue of control mice, small K5M-NM-^TNM-NM-2cat hyperplasia, large K5M-NM-^TNM-NM-2cat hyperplasia and K5M-NM-^TNM-NM-2cat tumor

Project description:Basal-like breast cancer is a heterogeneous disease characterised by the expression of basal cell markers, no oestrogen or progesterone receptor expression and a lack of HER2 overexpression. Recent studies have linked activation of the Wnt/beta-catenin pathway to basal-like breast cancer. Transgenic mice expressing N-terminally truncated stabilised beta-catenin in the mammary basal/myoepithelial cell layer (K5deltaNbetacat strain) develop mammary hyperplasias that progress to invasive carcinomas. Histological and microarray analyses of these lesions have revealed their high similarity to a subset of basal-like human breast tumours with squamous differentiation. As in human basal-like carcinomas, the Myc pathway was found to be activated in the mammary lesions of K5deltaNbetacat mice. Mammosphere and transplantation assays showed that a basal cell population with stem/progenitor characteristics was amplified in K5deltaNbetacat mouse preneoplastic glands. Myc deletion from the mammary basal layer of K5deltaNbetacat mice abolished both basal cell regenerative capacity and tumorigenesis. These results show that Myc is essential for beta-catenin-induced stem cell amplification and tumorigenesis and that basal stem/progenitor cells may be at the origin of a subset of basal-like breast tumours. mammary tissue from K5M-NM-^TNM-NM-2cat mice were dissected at successive stages of development (small hyperplasia (n=5), large hyperplasia (n=5), tumor (n=11) and control (n=4)) for RNA extraction and hybridization on Affymetrix microarrays

2013-12-31 | E-GEOD-43825 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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