ArticleBMC cancer2015
A pooled shRNA screen for regulators of primary mammary stem and progenitor cells identifies roles for Asap1 and Prox1.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- The Human Male Mammary Gland has Similar Epithelial Populations to Female but Distinct Composition and Transcriptional Properties.bioRxiv : the preprint server for biology · 2026Article
- Dividing out quantification uncertainty enables assessment of differential transcript usage with limma and edgeR.Nucleic acids research · 2025Article
- OmicNavigator: open-source software for the exploration, visualization, and archival of omic studies.BMC bioinformatics · 2024Article
- Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling.Nature communications · 2024Article
- Prox1 Suppresses the Proliferation of Breast Cancer Cells via Direct Inhibition of c-Myc Gene Expression.Cells · 2023Article
- Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma.Research (Washington, D.C.) · 2023Article
- Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas.Nature communications · 2022Article
- In vivo genome-editing screen identifies tumor suppressor genes that cooperate with Trp53 loss during mammary tumorigenesis.Molecular oncology · 2022Article
- Dashboard-style interactive plots for RNA-seq analysis are R Markdown ready withNAR genomics and bioinformatics · 2021Article
- Single cell transcriptome atlas of mouse mammary epithelial cells across development.Breast cancer research : BCR · 2021Article
- Optimal, Large-Scale Propagation of Mouse Mammary Tumor Organoids.Journal of mammary gland biology and neoplasia · 2020Article
- TET2 directs mammary luminal cell differentiation and endocrine response.Nature communications · 2020Article
- Covering all your bases: incorporating intron signal from RNA-seq data.NAR genomics and bioinformatics · 2020Article
- Tissue-resident ductal macrophages survey the mammary epithelium and facilitate tissue remodelling.Nature cell biology · 2020Article
- In Utero Heat Stress Alters the Offspring Epigenome.Scientific reports · 2018Article
- PROX1 is a transcriptional regulator of MMP14.Scientific reports · 2018Article
- Frequent overexpression of AMAP1, an Arf6 effector in cell invasion, is characteristic of the MMTV-PyMT rather than the MMTV-Neu human breast cancer model.Cell communication and signaling : CCS · 2018Article
- Transcription factor compensation during mammary gland development in E2F knockout mice.PloS one · 2018Article
- Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling.Nature communications · 2017Article
- Combining multiple tools outperforms individual methods in gene set enrichment analyses.Bioinformatics (Oxford, England) · 2017Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe molecular regulators that orchestrate stem cell renewal, proliferation and differentiation along the mammary epithelial hierarchy remain poorly understood. Here we have performed a large-scale pooled RNAi screen in primary mouse mammary stem cell (MaSC)-enriched basal cells using 1295 shRNAs against genes principally involved in transcriptional regulation.
methodsMaSC-enriched basal cells transduced with lentivirus pools carrying shRNAs were maintained as non-adherent mammospheres, a system known to support stem and progenitor cells. Integrated shRNAs that altered culture kinetics were identified by next generation sequencing as relative frequency changes over time. RNA-seq-based expression profiling coupled with in vitro progenitor and in vivo transplantation assays was used to confirm a role for candidate genes in mammary stem and/or progenitor cells.
resultsUtilizing a mammosphere-based assay, the screen identified several candidate regulators. Although some genes had been previously implicated in mammary gland development, the vast majority of genes uncovered have no known function within the mammary gland. RNA-seq analysis of freshly purified primary mammary epithelial populations and short-term cultured mammospheres was used to confirm the expression of candidate regulators. Two genes, Asap1 and Prox1, respectively implicated in breast cancer metastasis and progenitor cell function in other systems, were selected for further analysis as their roles in the normal mammary gland were unknown. Both Prox1 and Asap1 were shown to act as negative regulators of progenitor activity in vitro, and Asap1 knock-down led to a marked increase in repopulating activity in vivo, implying a role in stem cell activity.
conclusionsThis study has revealed a number of novel genes that influence the activity or survival of mammary stem and/or progenitor cells. Amongst these, we demonstrate that Prox1 and Asap1 behave as negative regulators of mammary stem/progenitor function. Both of these genes have also been implicated in oncogenesis. Our findings provide proof of principle for the use of short-term cultured primary MaSC/basal cells in functional RNAi screens.
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