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Large field of view-spatially resolved transcriptomics at nanoscale resolution

Ao Chen, Sha Liao, Mengnan Cheng, Kailong Ma, Liang Wu, Yiwei Lai, Jin Yang, Wenjiao Li, Jiangshan Xu, View ORCID ProfileShijie Hao, Huifang Lu, Xi Chen, Xing Liu, Xin Huang, Feng Lin, Xiaoxuan Tang, Zhao Li, Yang Hong, Defeng Fu, Yujia Jiang, Jian Peng, Shuai Liu, Mengzhe Shen, Chuanyu Liu, Quanshui Li, Zhifeng Wang, Zhaohui Wang, Xin Huang, Yue Yuan, View ORCID ProfileGiacomo Volpe, Carl Ward, Pura Muñoz-Cánoves, Jean Paul Thiery, Fuxiang Zhao, Mei Li, Haoyan Kuang, Ou Wang, Haorong Lu, Bo Wang, Ming Ni, Wenwei Zhang, Feng Mu, Ye Yin, Huanming Yang, Michael Lisby, Richard J. Cornall, Mathias Uhlen, Miguel A. Esteban, Yuxiang Li, Longqi Liu, Xun Xu, Jian Wang
doi: https://doi.org/10.1101/2021.01.17.427004
Ao Chen
1BGI-ShenZhen, Shenzhen 518103, China
2Department of Biology, University of Copenhagen, Copenhagen DK-2200, Denmark
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Sha Liao
1BGI-ShenZhen, Shenzhen 518103, China
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Mengnan Cheng
1BGI-ShenZhen, Shenzhen 518103, China
3BGI Education Center, University of Chinese Academy of Sciences (CAS), Shenzhen 518083, China
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Kailong Ma
1BGI-ShenZhen, Shenzhen 518103, China
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Liang Wu
1BGI-ShenZhen, Shenzhen 518103, China
3BGI Education Center, University of Chinese Academy of Sciences (CAS), Shenzhen 518083, China
4Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen, Shenzhen 518120, China
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Yiwei Lai
5Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
6CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China
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Jin Yang
7MGI, BGI-Shenzhen, Shenzhen 518083, China
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Wenjiao Li
1BGI-ShenZhen, Shenzhen 518103, China
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Jiangshan Xu
1BGI-ShenZhen, Shenzhen 518103, China
3BGI Education Center, University of Chinese Academy of Sciences (CAS), Shenzhen 518083, China
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Shijie Hao
1BGI-ShenZhen, Shenzhen 518103, China
3BGI Education Center, University of Chinese Academy of Sciences (CAS), Shenzhen 518083, China
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  • ORCID record for Shijie Hao
Huifang Lu
1BGI-ShenZhen, Shenzhen 518103, China
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Xi Chen
1BGI-ShenZhen, Shenzhen 518103, China
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Xing Liu
1BGI-ShenZhen, Shenzhen 518103, China
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Xin Huang
3BGI Education Center, University of Chinese Academy of Sciences (CAS), Shenzhen 518083, China
7MGI, BGI-Shenzhen, Shenzhen 518083, China
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Feng Lin
1BGI-ShenZhen, Shenzhen 518103, China
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Xiaoxuan Tang
1BGI-ShenZhen, Shenzhen 518103, China
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Zhao Li
1BGI-ShenZhen, Shenzhen 518103, China
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Yang Hong
1BGI-ShenZhen, Shenzhen 518103, China
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Defeng Fu
1BGI-ShenZhen, Shenzhen 518103, China
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Yujia Jiang
1BGI-ShenZhen, Shenzhen 518103, China
8BGI College & Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450000, China
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Jian Peng
1BGI-ShenZhen, Shenzhen 518103, China
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Shuai Liu
1BGI-ShenZhen, Shenzhen 518103, China
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Mengzhe Shen
1BGI-ShenZhen, Shenzhen 518103, China
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Chuanyu Liu
1BGI-ShenZhen, Shenzhen 518103, China
9Shenzhen Bay Laboratory, Shenzhen 518000, China
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Quanshui Li
1BGI-ShenZhen, Shenzhen 518103, China
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Zhifeng Wang
1BGI-ShenZhen, Shenzhen 518103, China
4Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen, Shenzhen 518120, China
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Zhaohui Wang
1BGI-ShenZhen, Shenzhen 518103, China
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Xin Huang
1BGI-ShenZhen, Shenzhen 518103, China
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Yue Yuan
1BGI-ShenZhen, Shenzhen 518103, China
3BGI Education Center, University of Chinese Academy of Sciences (CAS), Shenzhen 518083, China
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Giacomo Volpe
5Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
6CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China
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  • ORCID record for Giacomo Volpe
Carl Ward
5Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
6CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China
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Pura Muñoz-Cánoves
10Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), ICREA and CIBERNED, Barcelona E-08003, Spain
11Spanish National Center on Cardiovascular Research (CNIC), Madrid E-28029, Spain
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Jean Paul Thiery
12Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China
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Fuxiang Zhao
1BGI-ShenZhen, Shenzhen 518103, China
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Mei Li
1BGI-ShenZhen, Shenzhen 518103, China
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Haoyan Kuang
1BGI-ShenZhen, Shenzhen 518103, China
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Ou Wang
1BGI-ShenZhen, Shenzhen 518103, China
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Haorong Lu
13China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China
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Bo Wang
13China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China
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Ming Ni
7MGI, BGI-Shenzhen, Shenzhen 518083, China
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Wenwei Zhang
1BGI-ShenZhen, Shenzhen 518103, China
14Shenzhen Key Laboratory of Neurogenomics, BGI-ShenZhen, Shenzhen 518103, China
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Feng Mu
7MGI, BGI-Shenzhen, Shenzhen 518083, China
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Ye Yin
15BGI Genomics, BGI-Shenzhen, Shenzhen 518083, China
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Huanming Yang
1BGI-ShenZhen, Shenzhen 518103, China
16James D. Watson Institute of Genome Sciences, Hangzhou 310058, China
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Michael Lisby
2Department of Biology, University of Copenhagen, Copenhagen DK-2200, Denmark
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Richard J. Cornall
17Medical Research Council Human Immunology Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom
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Mathias Uhlen
18Department of Protein Science, Science for Life Laboratory, KTH-Royal Institute of Technology, 17121 Stockholm, Sweden
19Department of Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden
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Miguel A. Esteban
1BGI-ShenZhen, Shenzhen 518103, China
5Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
6CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Guangzhou 510530, China
20Institute of Stem Cells and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
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  • For correspondence: miguelesteban@genomics.cn liyuxiang@genomics.cn liulongqi@genomics.cn xuxun@genomics.cn wangjian@genomics.cn
Yuxiang Li
1BGI-ShenZhen, Shenzhen 518103, China
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  • For correspondence: miguelesteban@genomics.cn liyuxiang@genomics.cn liulongqi@genomics.cn xuxun@genomics.cn wangjian@genomics.cn
Longqi Liu
1BGI-ShenZhen, Shenzhen 518103, China
9Shenzhen Bay Laboratory, Shenzhen 518000, China
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  • For correspondence: miguelesteban@genomics.cn liyuxiang@genomics.cn liulongqi@genomics.cn xuxun@genomics.cn wangjian@genomics.cn
Xun Xu
1BGI-ShenZhen, Shenzhen 518103, China
21Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen 518120, China
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  • For correspondence: miguelesteban@genomics.cn liyuxiang@genomics.cn liulongqi@genomics.cn xuxun@genomics.cn wangjian@genomics.cn
Jian Wang
1BGI-ShenZhen, Shenzhen 518103, China
16James D. Watson Institute of Genome Sciences, Hangzhou 310058, China
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  • For correspondence: miguelesteban@genomics.cn liyuxiang@genomics.cn liulongqi@genomics.cn xuxun@genomics.cn wangjian@genomics.cn
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ABSTRACT

High-throughput profiling of in situ gene expression represents a major advance towards the systematic understanding of tissue complexity. Applied with enough capture area and high sample throughput it will help to define the spatio-temporal dynamics of gene expression in tissues and organisms. Yet, current technologies have considerable bottlenecks that limit widespread application. Here, we have combined DNA nanoball (DNB) patterned array chips and in situ RNA capture to develop Stereo-seq (Spatio-Temporal Enhanced REsolution Omics-sequencing). This approach allows high sample throughput transcriptomic profiling of histological sections at unprecedented (nanoscale) resolution with areas expandable to centimeter scale, high sensitivity and homogenous capture rate. As proof of principle, we applied Stereo-seq to the adult mouse brain and sagittal sections of E11.5 and E16.5 mouse embryos. Thanks to its unique features and amenability to additional modifications, Stereo-seq can pave the way for the systematic spatially resolved-omics characterization of tissues and organisms.

Competing Interest Statement

The chip, procedure and applications of Stereo-seq are covered in pending patents. Employees of BGI have stock holdings in BGI.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted January 24, 2021.
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Large field of view-spatially resolved transcriptomics at nanoscale resolution
Ao Chen, Sha Liao, Mengnan Cheng, Kailong Ma, Liang Wu, Yiwei Lai, Jin Yang, Wenjiao Li, Jiangshan Xu, Shijie Hao, Huifang Lu, Xi Chen, Xing Liu, Xin Huang, Feng Lin, Xiaoxuan Tang, Zhao Li, Yang Hong, Defeng Fu, Yujia Jiang, Jian Peng, Shuai Liu, Mengzhe Shen, Chuanyu Liu, Quanshui Li, Zhifeng Wang, Zhaohui Wang, Xin Huang, Yue Yuan, Giacomo Volpe, Carl Ward, Pura Muñoz-Cánoves, Jean Paul Thiery, Fuxiang Zhao, Mei Li, Haoyan Kuang, Ou Wang, Haorong Lu, Bo Wang, Ming Ni, Wenwei Zhang, Feng Mu, Ye Yin, Huanming Yang, Michael Lisby, Richard J. Cornall, Mathias Uhlen, Miguel A. Esteban, Yuxiang Li, Longqi Liu, Xun Xu, Jian Wang
bioRxiv 2021.01.17.427004; doi: https://doi.org/10.1101/2021.01.17.427004
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Large field of view-spatially resolved transcriptomics at nanoscale resolution
Ao Chen, Sha Liao, Mengnan Cheng, Kailong Ma, Liang Wu, Yiwei Lai, Jin Yang, Wenjiao Li, Jiangshan Xu, Shijie Hao, Huifang Lu, Xi Chen, Xing Liu, Xin Huang, Feng Lin, Xiaoxuan Tang, Zhao Li, Yang Hong, Defeng Fu, Yujia Jiang, Jian Peng, Shuai Liu, Mengzhe Shen, Chuanyu Liu, Quanshui Li, Zhifeng Wang, Zhaohui Wang, Xin Huang, Yue Yuan, Giacomo Volpe, Carl Ward, Pura Muñoz-Cánoves, Jean Paul Thiery, Fuxiang Zhao, Mei Li, Haoyan Kuang, Ou Wang, Haorong Lu, Bo Wang, Ming Ni, Wenwei Zhang, Feng Mu, Ye Yin, Huanming Yang, Michael Lisby, Richard J. Cornall, Mathias Uhlen, Miguel A. Esteban, Yuxiang Li, Longqi Liu, Xun Xu, Jian Wang
bioRxiv 2021.01.17.427004; doi: https://doi.org/10.1101/2021.01.17.427004

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