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.
The spinal cord is an assembly of spatially organized multicomponent cells that coordinates the transmission of motor, sensory and autonomic nerve functions. Although complex pathological and cellular alterations in spinal cord injury (SCI) have been documented, the spatiotemporal architecture of the molecular events that drive the injury progression remains poorly understood. Here, we conducted a spatially resolved transcriptomic profiling of gene expression in a mouse model of SCI, which demonstrated the comprehensive gene co-expression networks and transcriptional programs underlying the anatomic disorganization induced by SCI. Further, with integration of the single-cell RNA-sequencing datasets, we delineated the exquisite orchestration of multicellular transcriptional programs and in situ cell-cell interactions following SCI, and discerned regional diversity of astrocyte populations in intact and injured spinal tissues. The spatial molecular features endow the cell types with new biological significance, showcased by the identification of a distinct, SCI-induced population of astrocytes that exhibit functional heterogeneity in promoting both beneficial neuro/synapto-supportive and deleterious pro-inflammatory programs. Together, our dataset and analysis provide a rich resource and a spatiotemporal molecular atlas that potentially disentangle the cell organization in mammalian SCI and advance the injury management.
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