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Ductal keratin 15 luminal progenitors in normal breast exhibit a basal-like breast cancer transcriptomic signature.

作者信息

Kohler Katharina Theresa, Goldhammer Nadine, Demharter Samuel, Pfisterer Ulrich, Khodosevich Konstantin, Rønnov-Jessen Lone, Petersen Ole William, Villadsen René, Kim Jiyoung

机构信息

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.

出版信息

NPJ Breast Cancer. 2022 Jul 12;8(1):81. doi: 10.1038/s41523-022-00444-8.


DOI:10.1038/s41523-022-00444-8
PMID:35821504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9276673/
Abstract

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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/9276673/baed5d6a5752/41523_2022_444_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/9276673/a5a2ae9e03d4/41523_2022_444_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/9276673/9389f788ce5e/41523_2022_444_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/9276673/6ddf4e767cb1/41523_2022_444_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/9276673/baed5d6a5752/41523_2022_444_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/9276673/a5a2ae9e03d4/41523_2022_444_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/9276673/9389f788ce5e/41523_2022_444_Fig2a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/9276673/6ddf4e767cb1/41523_2022_444_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24ae/9276673/baed5d6a5752/41523_2022_444_Fig4_HTML.jpg

相似文献

[1]
Ductal keratin 15 luminal progenitors in normal breast exhibit a basal-like breast cancer transcriptomic signature.

NPJ Breast Cancer. 2022-7-12

[2]
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[3]
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[4]
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[8]
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[9]
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[10]
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Breast Cancer Res. 2016-11-3

引用本文的文献

[1]
Spatial transcriptomics in breast cancer: providing insight into tumor heterogeneity and promoting individualized therapy.

Front Immunol. 2024-12-19

[2]
Oncogene activated human breast luminal progenitors contribute basally located myoepithelial cells.

Breast Cancer Res. 2024-12-18

[3]
Differential chromatin accessibility and transcriptional dynamics define breast cancer subtypes and their lineages.

Nat Cancer. 2024-11

[4]
Mcam stabilizes a luminal progenitor-like breast cancer cell state via Ck2 control and Src/Akt/Stat3 attenuation.

NPJ Breast Cancer. 2024-9-14

[5]
Luminal progenitor and mature cells are more susceptible than basal cells to radiation-induced DNA double-strand breaks in rat mammary tissue.

J Radiat Res. 2024-9-24

[6]
ELF5: A Molecular Clock for Breast Aging and Cancer Susceptibility.

Cancers (Basel). 2024-1-19

[7]
Silencing of keratin 15 impairs viability and mobility while facilitating the doxorubicin chemosensitivity by inactivating the β‑catenin pathway in liver cancer.

Oncol Lett. 2023-8-30

[8]
SSEA-1 Correlates With the Invasive Phenotype in Breast Cancer.

J Histochem Cytochem. 2023-8

本文引用的文献

[1]
Myoepithelial progenitors as founder cells of hyperplastic human breast lesions upon PIK3CA transformation.

Commun Biol. 2022-3-10

[2]
Evidence for accelerated aging in mammary epithelia of women carrying germline or mutations.

Nat Aging. 2021-9

[3]
A new approach to breast cancer terminology based on the anatomic site of tumour origin: The importance of radiologic imaging biomarkers.

Eur J Radiol. 2022-4

[4]
A single-cell and spatially resolved atlas of human breast cancers.

Nat Genet. 2021-9

[5]
A Machine Learning Approach to Differentiate Two Specific Breast Cancer Subtypes Using Androgen Receptor Pathway Genes.

Technol Cancer Res Treat. 2021

[6]
High-throughput surface marker screen on primary human breast tissues reveals further cellular heterogeneity.

Breast Cancer Res. 2021-6-13

[7]
Mammary cell gene expression atlas links epithelial cell remodeling events to breast carcinogenesis.

Commun Biol. 2021-6-2

[8]
A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast.

EMBO J. 2021-6-1

[9]
A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells.

Cell Rep Med. 2021-3-16

[10]
Single-Cell RNA Sequencing of a Postmenopausal Normal Breast Tissue Identifies Multiple Cell Types That Contribute to Breast Cancer.

Cancers (Basel). 2020-12-4

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