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Cells and tissues are exquisitely organized in a complex but ordered manner to form organs and bodies so that individuals can function properly. The spatial organization and tissue architecture represent a keynote property underneath all living organisms. Molecular architecture and cellular composition within intact tissues play a vital role in a variety of biological processes, such as forming the complicated tissue functionality, precise regulation of cell transition in all living activities, consolidation of central nervous system, cellular responses to immunological and pathological cues. To explore these biological events at a large scale and fine resolution, a genome-wide understanding of spatial cellular changes is essential. However, previous bulk RNA sequencing and single-cell RNA sequencing technologies could not obtain the important spatial information of tissues and cells, despite their ability to detect high content transcriptional changes. These limitations have prompted the development of numerous spatially resolved technologies which provide a new dimension to interrogate the regional gene expression, cellular microenvironment, anatomical heterogeneity and cell-cell interactions. Since the advent of spatial transcriptomics, related works that use these technologies have increased rapidly, and new methods with higher throughput and resolution have grown quickly, all of which hold great promise to accelerate new discoveries in understanding the biological complexity. In this review, we briefly discussed the historical evolution of spatially resolved transcriptome. We broadly surveyed the representative methods. Furthermore, we summarized the general computational analysis pipeline for the spatial gene expression data. Finally, we proposed perspectives for technological development of spatial multi-omics.


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Spatial transcriptomics: new dimension of understanding biological complexity

Show Author's information Zhuxia Li1,4Guangdun Peng1,2,3( )
Ceter for Cell Lineage and Development, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China
Center for Cell Lineage and Atlas, Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
University of Chinese Academy of Sciences, Beijing 100049, China

Abstract

Cells and tissues are exquisitely organized in a complex but ordered manner to form organs and bodies so that individuals can function properly. The spatial organization and tissue architecture represent a keynote property underneath all living organisms. Molecular architecture and cellular composition within intact tissues play a vital role in a variety of biological processes, such as forming the complicated tissue functionality, precise regulation of cell transition in all living activities, consolidation of central nervous system, cellular responses to immunological and pathological cues. To explore these biological events at a large scale and fine resolution, a genome-wide understanding of spatial cellular changes is essential. However, previous bulk RNA sequencing and single-cell RNA sequencing technologies could not obtain the important spatial information of tissues and cells, despite their ability to detect high content transcriptional changes. These limitations have prompted the development of numerous spatially resolved technologies which provide a new dimension to interrogate the regional gene expression, cellular microenvironment, anatomical heterogeneity and cell-cell interactions. Since the advent of spatial transcriptomics, related works that use these technologies have increased rapidly, and new methods with higher throughput and resolution have grown quickly, all of which hold great promise to accelerate new discoveries in understanding the biological complexity. In this review, we briefly discussed the historical evolution of spatially resolved transcriptome. We broadly surveyed the representative methods. Furthermore, we summarized the general computational analysis pipeline for the spatial gene expression data. Finally, we proposed perspectives for technological development of spatial multi-omics.

Keywords: Single-cell sequencing, Spatial transcriptomics, Spatial data analysis, Spatial multi-omics, Histology

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Received: 01 August 2021
Accepted: 18 October 2021
Published: 21 January 2022
Issue date: June 2022

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© The Author(s) 2022

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Acknowledgements

We apologize to all authors whose work has not been cited in this review due to space constrains. We thank the critical reading from all the Peng lab members. This work was supported in part by National Key R&D Program of China (2018YFA0801402, 2018YFA0107200), the "Strategic Priority Research Program" of the Chinese Academy of Sciences (XDA16020404), National Natural Science Foundation of China (31871456), Guangdong Basic and Applied Basic Research Foundation (2019B151502054), Frontier Research Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory, 2018GZR110105013), Jiazi Research Innovative Project of Bioland Laboratory (2019GZR110108001), Science and Technology Planning Project of Guangdong Province (2020B1212060052).

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