A single-cell and spatially resolved atlas of human breast cancers

Sunny Z. Wu; Ghamdan Al-Eryani; Daniel Lee Roden; Simon Junankar; Kate Harvey; Alma Andersson; Aatish Thennavan; Chenfei Wang; James R. Torpy; Nenad Bartonicek; Taopeng Wang; Ludvig Larsson; Dominik Kaczorowski; Neil I. Weisenfeld; Cedric R. Uytingco; Jennifer G. Chew; Zachary W. Bent; Chia Ling Chan; Vikkitharan Gnanasambandapillai; Charles Antoine Dutertre; Laurence Gluch; Mun N. Hui; Jane Beith; Andrew Parker; Elizabeth Robbins; Davendra Segara; Caroline Cooper; Cindy Mak; Belinda Chan; Sanjay Warrier; Florent Ginhoux; Ewan Millar; Joseph E. Powell; Stephen R. Williams; X. Shirley Liu; Sandra O’Toole; Elgene Lim; Joakim Lundeberg; Charles M. Perou; Alexander Swarbrick

doi:10.1038/s41588-021-00911-1

A single-cell and spatially resolved atlas of human breast cancers

Sunny Z. Wu, Ghamdan Al-Eryani, Daniel Lee Roden, Simon Junankar, Kate Harvey, Alma Andersson, Aatish Thennavan, Chenfei Wang, James R. Torpy, Nenad Bartonicek, Taopeng Wang, Ludvig Larsson, Dominik Kaczorowski, Neil I. Weisenfeld, Cedric R. Uytingco, Jennifer G. Chew, Zachary W. Bent, Chia Ling Chan, Vikkitharan Gnanasambandapillai, Charles Antoine DutertreLaurence Gluch, Mun N. Hui, Jane Beith, Andrew Parker, Elizabeth Robbins, Davendra Segara, Caroline Cooper, Cindy Mak, Belinda Chan, Sanjay Warrier, Florent Ginhoux, Ewan Millar, Joseph E. Powell, Stephen R. Williams, X. Shirley Liu, Sandra O’Toole, Elgene Lim, Joakim Lundeberg, Charles M. Perou, Alexander Swarbrick

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

554 Citations (Scopus)

Abstract

Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization is limited. Here we present a single-cell and spatially resolved transcriptomics analysis of human breast cancers. We developed a single-cell method of intrinsic subtype classification (SCSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) provides high-resolution immune profiles, including new PD-L1/PD-L2⁺ macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell-surface protein expression through differentiation within three major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into antitumor immune regulation. Using single-cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer.

Original language	English
Pages (from-to)	1334-1347
Number of pages	14
Journal	Nature Genetics
Volume	53
Issue number	9
DOIs	https://doi.org/10.1038/s41588-021-00911-1
Publication status	Published - 1 Sept 2021
Externally published	Yes

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Wu, S. Z., Al-Eryani, G., Roden, D. L., Junankar, S., Harvey, K., Andersson, A., Thennavan, A., Wang, C., Torpy, J. R., Bartonicek, N., Wang, T., Larsson, L., Kaczorowski, D., Weisenfeld, N. I., Uytingco, C. R., Chew, J. G., Bent, Z. W., Chan, C. L., Gnanasambandapillai, V., ... Swarbrick, A. (2021). A single-cell and spatially resolved atlas of human breast cancers. Nature Genetics, 53(9), 1334-1347. https://doi.org/10.1038/s41588-021-00911-1

@article{28168392448542c58485eb3543940d5c,

title = "A single-cell and spatially resolved atlas of human breast cancers",

abstract = "Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization is limited. Here we present a single-cell and spatially resolved transcriptomics analysis of human breast cancers. We developed a single-cell method of intrinsic subtype classification (SCSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) provides high-resolution immune profiles, including new PD-L1/PD-L2+ macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell-surface protein expression through differentiation within three major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into antitumor immune regulation. Using single-cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed {\textquoteleft}ecotypes{\textquoteright}, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer.",

author = "Wu, {Sunny Z.} and Ghamdan Al-Eryani and Roden, {Daniel Lee} and Simon Junankar and Kate Harvey and Alma Andersson and Aatish Thennavan and Chenfei Wang and Torpy, {James R.} and Nenad Bartonicek and Taopeng Wang and Ludvig Larsson and Dominik Kaczorowski and Weisenfeld, {Neil I.} and Uytingco, {Cedric R.} and Chew, {Jennifer G.} and Bent, {Zachary W.} and Chan, {Chia Ling} and Vikkitharan Gnanasambandapillai and Dutertre, {Charles Antoine} and Laurence Gluch and Hui, {Mun N.} and Jane Beith and Andrew Parker and Elizabeth Robbins and Davendra Segara and Caroline Cooper and Cindy Mak and Belinda Chan and Sanjay Warrier and Florent Ginhoux and Ewan Millar and Powell, {Joseph E.} and Williams, {Stephen R.} and Liu, {X. Shirley} and Sandra O{\textquoteright}Toole and Elgene Lim and Joakim Lundeberg and Perou, {Charles M.} and Alexander Swarbrick",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2021",

month = sep,

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doi = "10.1038/s41588-021-00911-1",

language = "English",

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Wu, SZ, Al-Eryani, G, Roden, DL, Junankar, S, Harvey, K, Andersson, A, Thennavan, A, Wang, C, Torpy, JR, Bartonicek, N, Wang, T, Larsson, L, Kaczorowski, D, Weisenfeld, NI, Uytingco, CR, Chew, JG, Bent, ZW, Chan, CL, Gnanasambandapillai, V, Dutertre, CA, Gluch, L, Hui, MN, Beith, J, Parker, A, Robbins, E, Segara, D, Cooper, C, Mak, C, Chan, B, Warrier, S, Ginhoux, F, Millar, E, Powell, JE, Williams, SR, Liu, XS, O’Toole, S, Lim, E, Lundeberg, J, Perou, CM & Swarbrick, A 2021, 'A single-cell and spatially resolved atlas of human breast cancers', Nature Genetics, vol. 53, no. 9, pp. 1334-1347. https://doi.org/10.1038/s41588-021-00911-1

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T1 - A single-cell and spatially resolved atlas of human breast cancers

AU - Wu, Sunny Z.

AU - Al-Eryani, Ghamdan

AU - Roden, Daniel Lee

AU - Junankar, Simon

AU - Harvey, Kate

AU - Andersson, Alma

AU - Thennavan, Aatish

AU - Wang, Chenfei

AU - Torpy, James R.

AU - Bartonicek, Nenad

AU - Wang, Taopeng

AU - Larsson, Ludvig

AU - Kaczorowski, Dominik

AU - Weisenfeld, Neil I.

AU - Uytingco, Cedric R.

AU - Chew, Jennifer G.

AU - Bent, Zachary W.

AU - Chan, Chia Ling

AU - Gnanasambandapillai, Vikkitharan

AU - Dutertre, Charles Antoine

AU - Gluch, Laurence

AU - Hui, Mun N.

AU - Beith, Jane

AU - Parker, Andrew

AU - Robbins, Elizabeth

AU - Segara, Davendra

AU - Cooper, Caroline

AU - Mak, Cindy

AU - Chan, Belinda

AU - Warrier, Sanjay

AU - Ginhoux, Florent

AU - Millar, Ewan

AU - Powell, Joseph E.

AU - Williams, Stephen R.

AU - Liu, X. Shirley

AU - O’Toole, Sandra

AU - Lim, Elgene

AU - Lundeberg, Joakim

AU - Perou, Charles M.

AU - Swarbrick, Alexander

PY - 2021/9/1

Y1 - 2021/9/1

N2 - Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization is limited. Here we present a single-cell and spatially resolved transcriptomics analysis of human breast cancers. We developed a single-cell method of intrinsic subtype classification (SCSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) provides high-resolution immune profiles, including new PD-L1/PD-L2+ macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell-surface protein expression through differentiation within three major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into antitumor immune regulation. Using single-cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer.

AB - Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization is limited. Here we present a single-cell and spatially resolved transcriptomics analysis of human breast cancers. We developed a single-cell method of intrinsic subtype classification (SCSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) provides high-resolution immune profiles, including new PD-L1/PD-L2+ macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell-surface protein expression through differentiation within three major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into antitumor immune regulation. Using single-cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer.

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U2 - 10.1038/s41588-021-00911-1

DO - 10.1038/s41588-021-00911-1

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C2 - 34493872

AN - SCOPUS:85114607983

SN - 1061-4036

VL - 53

SP - 1334

EP - 1347

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

A single-cell and spatially resolved atlas of human breast cancers

Abstract

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