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

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

PROVIDER: PRJNA756977 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15566611_1.fastq.gz	Fastqsanger.gz
	SRR15566611_2.fastq.gz	Fastqsanger.gz
	SRR15566612_1.fastq.gz	Fastqsanger.gz
	SRR15566612_2.fastq.gz	Fastqsanger.gz

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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.

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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.

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

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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.

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