Kohler Katharina Theresa, Goldhammer Nadine, Demharter Samuel, Pfisterer Ulrich, Khodosevich Konstantin, Rønnov-Jessen Lone, Petersen Ole William, Villadsen René, Kim Jiyoung
Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen N, Denmark.
Novo Nordisk Foundation Center for Stem Cell Biology, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen N, Denmark.
NPJ Breast Cancer. 2022 Jul 12;8(1):81. doi: 10.1038/s41523-022-00444-8.
Normal breast luminal epithelial progenitors have been implicated as cell of origin in basal-like breast cancer, but their anatomical localization remains understudied. Here, we combine collection under the microscope of organoids from reduction mammoplasties and single-cell mRNA sequencing (scRNA-seq) of FACS-sorted luminal epithelial cells with multicolor imaging to profile ducts and terminal duct lobular units (TDLUs) and compare them with breast cancer subtypes. Unsupervised clustering reveals eleven distinct clusters and a differentiation trajectory starting with keratin 15 (K15) progenitors enriched in ducts. Spatial mapping of luminal progenitors is confirmed at the protein level by staining with critical duct markers. Comparison of the gene expression profiles of normal luminal cells with those of breast cancer subtypes suggests a strong correlation between normal breast ductal progenitors and basal-like breast cancer. We propose that K15 basal-like breast cancers originate in ductal progenitors, which emphasizes the importance of not only lineages but also cellular position within the ductal-lobular tree.
Breast Cancer Res. 2020-9-29
Proc Natl Acad Sci U S A. 2017-11-6
Breast Cancer Res. 2016-11-3
Breast Cancer Res. 2024-12-18
Cancers (Basel). 2024-1-19
J Histochem Cytochem. 2023-8
Nat Genet. 2021-9
Technol Cancer Res Treat. 2021
Breast Cancer Res. 2021-6-13