XYZeq: Spatially resolved single-cell RNA sequencing reveals expression heterogeneity in the tumor microenvironment

被引：75

作者：

Lee, Youjin ^{[1
,2
,3
,4
]}

Bogdanoff, Derek ^{[5
,6
]}

Wang, Yutong ^{[7
,8
]}

Hartoularos, George C. ^{[9
,12
,21
]}

Woo, Jonathan M. ^{[1
,2
,3
,4
]}

Mowery, Cody T. ^{[1
,2
,3
,4
,10
,11
]}

Nisonoff, Hunter M. ^{[8
]}

Lee, David S. ^{[3
,12
,21
]}

Sun, Yang ^{[3
,12
,21
]}

Lee, James ^{[13
]}

Mehdizadeh, Sadaf ^{[2
]}

Cantlon, Joshua ^{[14
]}

Shifrut, Eric ^{[1
,2
,3
,4
]}

Ngyuen, David N. ^{[1
,2
,3
,4
,5
]}

Roth, Theodore L. ^{[1
,2
,3
,10
,11
]}

Song, Yun S. ^{[16
,17
,18
]}

Marson, Alexander ^{[1
,2
,3
,4
,15
,18
,19
,20
,21
,22
]}

Chow, Eric D. ^{[5
,6
]}

Ye, Chun Jimmie ^{[12
,18
,20
,21
,22
,23
,24
]}

机构：

[1] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 USA

[3] Univ Calif Berkeley, Innovat Genom Inst, Berkeley, CA 94720 USA

[4] J David Gladstone Inst, San Francisco, CA 94158 USA

[5] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA

[6] Univ Calif San Francisco, Ctr Adv Technol, San Francisco, CA 94158 USA

[7] Univ Calif Berkeley, Grad Grp Biostat, Berkeley, CA 94720 USA

[8] Univ Calif Berkeley, Ctr Computat Biol, Berkeley, CA 94720 USA

[9] Univ Calif San Francisco, Grad Program Biol & Med Informat, San Francisco, CA 94158 USA

[10] Univ Calif San Francisco, Med Scientist Training Program, San Francisco, CA 94143 USA

[11] Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA

[12] Univ Calif San Francisco, Div Rheumatol, San Francisco, CA 94143 USA

[13] Univ Calif San Francisco, Div Hematol & Oncol, San Francisco, CA 94143 USA

[14] Scienion AG, Volmerstr 7b, D-12489 Berlin, Germany

[15] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[16] Univ Calif Berkeley, Comp Sci Div, Berkeley, CA 94720 USA

[17] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA

[18] Chan Zuckerberg Biohub, San Francisco, CA 94158 USA

[19] Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94158 USA

[20] Univ Calif San Francisco, Parker Inst Canc Immunotherapy, San Francisco, CA 94129 USA

[21] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA

[22] Gladstone UCSF Inst Genom Immunol, San Francisco, CA 94158 USA

[23] Univ Calif San Francisco, Inst Computat Hlth Sci, San Francisco, CA 94143 USA

[24] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA

来源：

SCIENCE ADVANCES | 2021年 / 7卷 / 17期

关键词：

D O I：

10.1126/sciadv.abg4755

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Single-cell RNA sequencing (scRNA-seq) of tissues has revealed remarkable heterogeneity of cell types and states but does not provide information on the spatial organization of cells. To better understand how individual cells function within an anatomical space, we developed XYZeq, a workflow that encodes spatial metadata into scRNAseq libraries. We used XYZeq to profile mouse tumor models to capture spatially barcoded transcriptomes from tens of thousands of cells. Analyses of these data revealed the spatial distribution of distinct cell types and a cell migration-associated transcriptomic program in tumor-associated mesenchymal stem cells (MSCs). Furthermore, we identify localized expression of tumor suppressor genes by MSCs that vary with proximity to the tumor core. We demonstrate that XYZeq can be used to map the transcriptome and spatial localization of individual cells in situ to reveal how cell composition and cell states can be affected by location within complex pathological tissue.

引用

页数：14

共 51 条

[1] High-throughput spatial mapping of single-cell RNA-seq data to tissue of origin [J].

Achim, Kaia ;

Pettit, Jean-Baptiste ;

Saraiva, Luis R. ;

Gavriouchkina, Daria ;

Larsson, Tomas ;

Arendt, Detlev ;

Marioni, John C. .

NATURE BIOTECHNOLOGY, 2015, 33 (05) :503-U215

[2] A practical solution for preserving single cells for RNA sequencing [J].

Attar, Moustafa ;

Sharma, Eshita ;

Li, Shuqiang ;

Bryer, Claire ;

Cubitt, Laura ;

Broxholme, John ;

Lockstone, Helen ;

Kinchen, James ;

Simmons, Alison ;

Piazza, Paolo ;

Buck, David ;

Livak, Kenneth J. ;

Bowden, Rory .

SCIENTIFIC REPORTS, 2018, 8

[3] The Impact of Varying Cooling and Thawing Rates on the Quality of Cryopreserved Human Peripheral Blood T Cells [J].

Baboo, Jasmin ;

Kilbride, Peter ;

Delahaye, Mike ;

Milne, Stuart ;

Fonseca, Fernanda ;

Blanco, Magdalena ;

Meneghel, Julie ;

Nancekievill, Alex ;

Gaddum, Nick ;

Morris, G. John .

SCIENTIFIC REPORTS, 2019, 9 (1)

[4] Comprehensive single-cell transcriptional profiling of a multicellular organism [J].

Cao, Junyue ;

Packer, Jonathan S. ;

Ramani, Vijay ;

Cusanovich, Darren A. ;

Huynh, Chau ;

Daza, Riza ;

Qiu, Xiaojie ;

Lee, Choli ;

Furlan, Scott N. ;

Steemers, Frank J. ;

Adey, Andrew ;

Waterston, Robert H. ;

Trapnell, Cole ;

Shendure, Jay .

SCIENCE, 2017, 357 (6352) :661-667

[5] Biclustering of gene expression data by non-smooth non-negative matrix factorization [J].

Carmona-Saez, P ;

Pascual-Marqui, RD ;

Tirado, F ;

Carazo, JM ;

Pascual-Montano, A .

BMC BIOINFORMATICS, 2006, 7 (1)

[6] Spatially resolved, highly multiplexed RNA profiling in single cells [J].

Chen, Kok Hao ;

Boettiger, Alistair N. ;

Moffitt, Jeffrey R. ;

Wang, Siyuan ;

Zhuang, Xiaowei .

SCIENCE, 2015, 348 (6233)

[7] Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation [J].

Costa Jordao, Marta Joana ;

Sankowski, Roman ;

Brendecke, Stefanie M. ;

Sagar ;

Locatelli, Giuseppe ;

Tai, Yi-Heng ;

Tay, Tuan Leng ;

Schramm, Eva ;

Armbruster, Stephan ;

Hagemeyer, Nora ;

Gross, Olaf ;

Mai, Dominic ;

Cicek, Ozgun ;

Falk, Thorsten ;

Kerschensteiner, Martin ;

Grun, Dominic ;

Prinz, Marco .

SCIENCE, 2019, 363 (6425) :365-+

[8]

DING J, 2020, NAT BIOTECHNOL, V38, P737, DOI DOI 10.1038/S41587-020-0465-8

[9] GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists [J].

Eden, Eran ;

Navon, Roy ;

Steinfeld, Israel ;

Lipson, Doron ;

Yakhini, Zohar .

BMC BIOINFORMATICS, 2009, 10

[10] Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution [J].

Efremova, Mirjana ;

Rieder, Dietmar ;

Klepsch, Victoria ;

Charoentong, Pornpimol ;

Finotello, Francesca ;

Hackl, Hubert ;

Hermann-Kleiter, Natascha ;

Loewer, Martin ;

Baier, Gottfried ;

Krogsdam, Anne ;

Trajanoski, Zlatko .

NATURE COMMUNICATIONS, 2018, 9

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