Three-dimensional imaging mass cytometry for highly multiplexed molecular and cellular mapping of tissues and the tumor microenvironment

Sohrab P. Shah, Xiaowei Zhuang, Carlos Caldas, Dario Bressan, Giorgia Battistoni, Gregory J. Hannon, Daniel Goodwin, Anubhav Sinha, Shahar Alon, Edward A. Fisher, Holger Moch, Bernd Bodenmiller, Shankar Balasubramanian, Ping Zheng, Andrew McPherson, Samuel Aparício, Ignacio Vázquez-Garćıa, H. Raza Ali, Raúl Catena, A. Yoldaş, Neal L. Millar, Kirsty Sawicka, Oscar M. Rueda, Andrew Roth, Johanna A. Joyce, Daniel Lai, Natalie de Souza, Asmamaw T. Wassie, D. Lai, E. Laks, S. P. Shah, A. Shea, P. Zheng, X. Zhuang, Alejandra Bruna, Marta Pàez‐Ribes, N. A. Walton, B. Bodenmiller, Leonardo A. Sepúlveda, Maurizio Callari, L. Kuett, Emma Laks, Ian G. Cannell, Cristina Jauset, Claire M. Mulvey, Fatime Qosaj, Ciara H. O’Flanagan, Marcel Burger, Sandra Tietscher, Emmanouil D. Karagiannis, Wendy Greenwood, Giulia Lerda, Abigail Shea, Spencer S. Watson, Jonas Windhager, Russell Kunes, A. Dariush, M. Al Sa’d, Robert Becker, E. S. Boyden, Helen Casbolt, N. Chornay, K. Dinh, A. Emenari, Y. Eyal-Lubling, E. A. González-Solares, C. Gónzalez-Fernández, Francesco Grimaldi, Shelley Harris, Laura Kuett, M. Lee, Y. Li, I. Pearsall, Tamara Ruiz, Adrian L. Smith, Siegfried Vogl, Sonja Wild, C. Xia, Ali Fatemi, Tatjana Kovačević, S. Tavaré, Joanna Weselak, Elyse T. Williams, Alaz Özcan, Alex Plüss, Y. Cui, Joy Linyue Fan, H. Lee, I. Nugent, Peter Schraml

2021-12-24

SCID: 54.1/7eysdv2f

Abstract (AI)

A holistic understanding of tissue and organ structure and function requires the detection of molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous detection of up to 40 antigens and transcripts using metal-tagged antibodies but has so far been restricted to two-dimensional imaging. Here we report the development of 3D IMC for multiplexed 3D tissue analysis at single-cell resolution and demonstrate the utility of the technology by analysis of human breast cancer samples. The resulting 3D models reveal cellular and microenvironmental heterogeneity and cell-level tissue organization not detectable in two dimensions. 3D IMC will prove powerful in the study of phenomena occurring in 3D space such as tumor cell invasion and is expected to provide invaluable insights into cellular microenvironments and tissue architecture.

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DOI

10.1038/s43018-021-00301-w

Publication Date

2021-12-24

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Authors

Sohrab P. Shah

Xiaowei Zhuang

Carlos Caldas

Dario Bressan

Giorgia Battistoni

Gregory J. Hannon

Daniel Goodwin

Anubhav Sinha

Shahar Alon

Edward A. Fisher

Holger Moch

Bernd Bodenmiller

Shankar Balasubramanian

Ping Zheng

Andrew McPherson

Samuel Aparício

Ignacio Vázquez-Garćıa

H. Raza Ali

Raúl Catena

A. Yoldaş

Neal L. Millar

Kirsty Sawicka

Oscar M. Rueda

Andrew Roth

Johanna A. Joyce

Daniel Lai

Natalie de Souza

Asmamaw T. Wassie

D. Lai

E. Laks

S. P. Shah

A. Shea

P. Zheng

X. Zhuang

Alejandra Bruna

Marta Pàez‐Ribes

N. A. Walton

B. Bodenmiller

Leonardo A. Sepúlveda

Maurizio Callari

L. Kuett

Emma Laks

Ian G. Cannell

Cristina Jauset

Claire M. Mulvey

Fatime Qosaj

Ciara H. O’Flanagan

Marcel Burger

Sandra Tietscher

Emmanouil D. Karagiannis

Wendy Greenwood

Giulia Lerda

Abigail Shea

Spencer S. Watson

Jonas Windhager

Russell Kunes

A. Dariush

M. Al Sa’d

Robert Becker

E. S. Boyden

Helen Casbolt

N. Chornay

K. Dinh

A. Emenari

Y. Eyal-Lubling

E. A. González-Solares

C. Gónzalez-Fernández

Francesco Grimaldi

Shelley Harris

Laura Kuett

M. Lee

Y. Li

I. Pearsall

Tamara Ruiz

Adrian L. Smith

Siegfried Vogl

Sonja Wild

C. Xia

Ali Fatemi

Tatjana Kovačević

S. Tavaré

Joanna Weselak

Elyse T. Williams

Alaz Özcan

Alex Plüss

Y. Cui

Joy Linyue Fan

H. Lee

I. Nugent

Peter Schraml

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