Ductal keratin 15+ luminal progenitors in normal breast exhibit a basal-like breast cancer transcriptomic signature
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Ductal keratin 15+ luminal progenitors in normal breast exhibit a basal-like breast cancer transcriptomic signature. / Kohler, Katharina Theresa; Goldhammer, Nadine; Demharter, Samuel; Pfisterer, Ulrich; Khodosevich, Konstantin; Rønnov-Jessen, Lone; Petersen, Ole William; Villadsen, René; Kim, Jiyoung.
In: npj Breast Cancer, Vol. 8, No. 1, 81, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Ductal keratin 15+ luminal progenitors in normal breast exhibit a basal-like breast cancer transcriptomic signature
AU - Kohler, Katharina Theresa
AU - Goldhammer, Nadine
AU - Demharter, Samuel
AU - Pfisterer, Ulrich
AU - Khodosevich, Konstantin
AU - Rønnov-Jessen, Lone
AU - Petersen, Ole William
AU - Villadsen, René
AU - Kim, Jiyoung
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41523-022-00444-8
DO - 10.1038/s41523-022-00444-8
M3 - Journal article
C2 - 35821504
AN - SCOPUS:85133902399
VL - 8
JO - npj Breast Cancer
JF - npj Breast Cancer
SN - 2374-4677
IS - 1
M1 - 81
ER -
ID: 314625952