ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype

Simon Junankar; Laura A. Baker; Daniel L. Roden; Radhika Nair; Ben Elsworth; David Gallego-Ortega; Paul Lacaze; Aurélie Cazet; Iva Nikolic; Wee Siang Teo; Jessica Yang; Andrea McFarland; Kate Harvey; Matthew J. Naylor; Sunil R. Lakhani; Peter T. Simpson; Ashwini Raghavendra; Jodi Saunus; Jason Madore; Ewan K. A. Millar

doi:10.1038/ncomms7548

ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype

Simon Junankar, Laura A. Baker, Daniel L. Roden, Radhika Nair, Ben Elsworth, David Gallego-Ortega, Paul Lacaze, Aurélie Cazet, Iva Nikolic, Wee Siang Teo, Jessica Yang, Andrea McFarland, Kate Harvey, Matthew J. Naylor, Sunil R. Lakhani, Peter T. Simpson, Ashwini Raghavendra, Jodi Saunus, Jason Madore, Ewan K. A. Millar

Research output: Contribution to journal › Article › peer-review

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Abstract

Basal-like breast cancer (BLBC) is a heterogeneous disease with poor prognosis; however, its cellular origins and aetiology are poorly understood. In this study, we show that inhibitor of differentiation 4 (ID4) is a key regulator of mammary stem cell self-renewal and marks a subset of BLBC with a putative mammary basal cell of origin. Using an ID4GFP knock-in reporter mouse and single-cell transcriptomics, we show that ID4 marks a stem cell-enriched subset of the mammary basal cell population. ID4 maintains the mammary stem cell pool by suppressing key factors required for luminal differentiation. Furthermore, ID4 is specifically expressed by a subset of human BLBC that possess a very poor prognosis and a transcriptional signature similar to a mammary stem cell. These studies identify ID4 as a mammary stem cell regulator, deconvolute the heterogeneity of BLBC and link a subset of mammary stem cells to the aetiology of BLBC.

Original language	English
Article number	6548
Number of pages	12
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7548
Publication status	Published - 2015

Keywords

breast cancer
mammary stem cells
phenotype

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms7548

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Junankar, S., Baker, L. A., Roden, D. L., Nair, R., Elsworth, B., Gallego-Ortega, D., Lacaze, P., Cazet, A., Nikolic, I., Teo, W. S., Yang, J., McFarland, A., Harvey, K., Naylor, M. J., Lakhani, S. R., Simpson, P. T., Raghavendra, A., Saunus, J., Madore, J., & Millar, E. K. A. (2015). ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype. Nature Communications, 6, Article 6548. https://doi.org/10.1038/ncomms7548

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title = "ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype",

abstract = "Basal-like breast cancer (BLBC) is a heterogeneous disease with poor prognosis; however, its cellular origins and aetiology are poorly understood. In this study, we show that inhibitor of differentiation 4 (ID4) is a key regulator of mammary stem cell self-renewal and marks a subset of BLBC with a putative mammary basal cell of origin. Using an ID4GFP knock-in reporter mouse and single-cell transcriptomics, we show that ID4 marks a stem cell-enriched subset of the mammary basal cell population. ID4 maintains the mammary stem cell pool by suppressing key factors required for luminal differentiation. Furthermore, ID4 is specifically expressed by a subset of human BLBC that possess a very poor prognosis and a transcriptional signature similar to a mammary stem cell. These studies identify ID4 as a mammary stem cell regulator, deconvolute the heterogeneity of BLBC and link a subset of mammary stem cells to the aetiology of BLBC.",

keywords = "breast cancer, mammary stem cells, phenotype",

author = "Simon Junankar and Baker, {Laura A.} and Roden, {Daniel L.} and Radhika Nair and Ben Elsworth and David Gallego-Ortega and Paul Lacaze and Aur{\'e}lie Cazet and Iva Nikolic and Teo, {Wee Siang} and Jessica Yang and Andrea McFarland and Kate Harvey and Naylor, {Matthew J.} and Lakhani, {Sunil R.} and Simpson, {Peter T.} and Ashwini Raghavendra and Jodi Saunus and Jason Madore and Millar, {Ewan K. A.}",

year = "2015",

doi = "10.1038/ncomms7548",

language = "English",

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journal = "Nature Communications",

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Junankar, S, Baker, LA, Roden, DL, Nair, R, Elsworth, B, Gallego-Ortega, D, Lacaze, P, Cazet, A, Nikolic, I, Teo, WS, Yang, J, McFarland, A, Harvey, K, Naylor, MJ, Lakhani, SR, Simpson, PT, Raghavendra, A, Saunus, J, Madore, J & Millar, EKA 2015, 'ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype', Nature Communications, vol. 6, 6548. https://doi.org/10.1038/ncomms7548

TY - JOUR

T1 - ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype

AU - Junankar, Simon

AU - Baker, Laura A.

AU - Roden, Daniel L.

AU - Nair, Radhika

AU - Elsworth, Ben

AU - Gallego-Ortega, David

AU - Lacaze, Paul

AU - Cazet, Aurélie

AU - Nikolic, Iva

AU - Teo, Wee Siang

AU - Yang, Jessica

AU - McFarland, Andrea

AU - Harvey, Kate

AU - Naylor, Matthew J.

AU - Lakhani, Sunil R.

AU - Simpson, Peter T.

AU - Raghavendra, Ashwini

AU - Saunus, Jodi

AU - Madore, Jason

AU - Millar, Ewan K. A.

PY - 2015

Y1 - 2015

N2 - Basal-like breast cancer (BLBC) is a heterogeneous disease with poor prognosis; however, its cellular origins and aetiology are poorly understood. In this study, we show that inhibitor of differentiation 4 (ID4) is a key regulator of mammary stem cell self-renewal and marks a subset of BLBC with a putative mammary basal cell of origin. Using an ID4GFP knock-in reporter mouse and single-cell transcriptomics, we show that ID4 marks a stem cell-enriched subset of the mammary basal cell population. ID4 maintains the mammary stem cell pool by suppressing key factors required for luminal differentiation. Furthermore, ID4 is specifically expressed by a subset of human BLBC that possess a very poor prognosis and a transcriptional signature similar to a mammary stem cell. These studies identify ID4 as a mammary stem cell regulator, deconvolute the heterogeneity of BLBC and link a subset of mammary stem cells to the aetiology of BLBC.

AB - Basal-like breast cancer (BLBC) is a heterogeneous disease with poor prognosis; however, its cellular origins and aetiology are poorly understood. In this study, we show that inhibitor of differentiation 4 (ID4) is a key regulator of mammary stem cell self-renewal and marks a subset of BLBC with a putative mammary basal cell of origin. Using an ID4GFP knock-in reporter mouse and single-cell transcriptomics, we show that ID4 marks a stem cell-enriched subset of the mammary basal cell population. ID4 maintains the mammary stem cell pool by suppressing key factors required for luminal differentiation. Furthermore, ID4 is specifically expressed by a subset of human BLBC that possess a very poor prognosis and a transcriptional signature similar to a mammary stem cell. These studies identify ID4 as a mammary stem cell regulator, deconvolute the heterogeneity of BLBC and link a subset of mammary stem cells to the aetiology of BLBC.

KW - breast cancer

KW - mammary stem cells

KW - phenotype

UR - http://handle.uws.edu.au:8081/1959.7/uws:30725

U2 - 10.1038/ncomms7548

DO - 10.1038/ncomms7548

M3 - Article

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

M1 - 6548

ER -

ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype

Abstract

Keywords

UN SDGs

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