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

50 Citations (Scopus)

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

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

breast cancer
mammary stem cells
phenotype

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10.1038/ncomms7548

Cite this

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

@article{c62f62f626ff406a908241c47bf0f7d2,

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

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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

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Keywords

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