ArticleNature communications2021
Time-resolved single-cell analysis of Brca1 associated mammary tumourigenesis reveals aberrant differentiation of luminal progenitors.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 84 citations in OpenAlex.
- Breast cancer prevention by prophylactic Lalba mRNA-LNP vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Runx1 and Runx2 act in concert to suppress Wnt/β-catenin-driven mammary tumourigenesis.British journal of cancer · 2026Article
- Mouse genetic mosaic model for basal-like breast cancer reveals disruption of basal-myoepithelial architecture at premalignancy.Research square · 2026Article
- Insights from three decades of BRCA1/2 modeling in mice.Nature genetics · 2026Review
- From mutation to treatment: The dual role of BRCA1 and BRCA2 in gynecological malignancy development and management a systematic review.Biochemistry and biophysics reports · 2026Review
- Interleukin-34-Induced Arg1+ Macrophages Play a Key Role in Breast Cancer Brain Metastasis.Cancer research communications · 2026Article
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- Necroptosis in both tumour and stromal compartments determines responsiveness to immunogenic cell death-based immunotherapy.Nature communications · 2026Article
- Rank signaling drives basal cell-lineage infidelity leading to mammary tumorigenesis.Nature communications · 2026Article
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- BRCA1: An Unrecognized Modulator of Lineage Plasticity in Basal-like Breast Cancer.Journal of mammary gland biology and neoplasia · 2025Review
- Review
- From lactation to malignancy: A comparison between healthy and cancerous breast gland at single-cell resolution reveals new issues for tumorigenesis.FEBS letters · 2025Article
- Defining breast epithelial cell types in the single-cell era.Developmental cell · 2025Review
- Dynamic clustering of genomics cohorts beyond race, ethnicity-and ancestry.BMC medical genomics · 2025Article
- Epigenomic disorder and partial EMT impair luminal progenitor integrity in Brca1-associated breast tumorigenesis.Molecular cancer · 2025Article
- Druggable Molecular Networks inBiology · 2025Review
- Cells-of-Origin of Breast Cancer and Intertumoral Heterogeneity.Advances in experimental medicine and biology · 2025Review
- Single-Cell Analysis in the Mouse and Human Mammary Gland.Advances in experimental medicine and biology · 2025Review
- Advancing Cancer Biology: Highlights from the 2025 FASEB SRC on Cellular Plasticity in Cancer.Cancer heterogeneity and plasticity · 2025Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
It is unclear how genetic aberrations impact the state of nascent tumour cells and their microenvironment. BRCA1 driven triple negative breast cancer (TNBC) has been shown to arise from luminal progenitors yet little is known about how BRCA1 loss-of-function (LOF) and concomitant mutations affect the luminal progenitor cell state. Here we demonstrate how time-resolved single-cell profiling of genetically engineered mouse models before tumour formation can address this challenge. We found that perturbing Brca1/p53 in luminal progenitors induces aberrant alveolar differentiation pre-malignancy accompanied by pro-tumourigenic changes in the immune compartment. Unlike alveolar differentiation during gestation, this process is cell autonomous and characterised by the dysregulation of transcription factors driving alveologenesis. Based on our data we propose a model where Brca1/p53 LOF inadvertently promotes 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.
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