1A Spatiotemporal Dynamic Immune Landscape of the COVID-19 Hamster Lung [Spatiotemporal]Source: STOmics DB (ID: STT0000006 )

Although SARS‐CoV‐2‐mediated inflammation has attracted global health concerns since 2019, its pulmonary immunopathology is not fully understood. Here we generated a comprehensive cellular and molecular landscape of healthy and COVID-19 hamster lungs at different timepoints after infection, using single-cell RNA sequencing and spatial transcriptomic sequencing to map the entire progression of COVID-19. We found SARS-CoV-2 could infect naïve T cells and induced cell death to decrease T cell number at the early stage of COVID-19. Besides, we observed the activation and depletion of tissue resident myeloid cells after infection, the accumulation of Isg12+Cst7+ neutrophils and Il10+Spp1+ M2-like macrophages to clean up virus and resolve inflammation. Finally, we identified Trem2+AM and Fbp1+AM subsets during the resolution stage of COVID-19. Our study provided spatiotemporally-resolved insights into the lung cells transcriptome, identified distinct tissue regions of viral infection, lung injury, repair and remodeling.

2Spatiotemporal transcriptomics elucidates the pathogenesis of fulminant viral myocarditisSource: STOmics DB (ID: STT0000127 )

Fulminant myocarditis (FM), a severe myocardial inflammatory disease, frequently leads to sudden death in young individuals. This study presents a comprehensive transcriptome analysis of coxsackievirus B3 (CVB3)-induced myocarditis in A/J mice, both pre- and post-treatment, utilizing single-cell and spatial transcriptomics at seven distinct time points. Our research uncovers the pivotal role of mesothelial cells in the pathogenesis of myocarditis, serving as the initial targets for CVB3 that subsequently activate macrophages, fostering an inflammatory environment. This activation cascade leads to the enrichment of macrophages and T cells in the affected myocardial regions, where they contribute to tissue damage through the development of pro-inflammatory 'Inflammatory_Mac' from peripheral monocytes. Moreover, our findings highlight the detrimental impact of Cd8+ effector T cells, which, upon releasing cytotoxic molecules, especially IFN-γ, modulate the expression of Spi1, driving cardiomyocyte death and further exacerbating the disease's progression. Targeting both IFN-γ and Spi1 yield positive treatment effects on FM mice. As an important immunomodulatory drug, Intravenous immunoglobulin (IVIG) treatment significantly reduced the death rate of FM mice, inhibits the proliferation of virus and suppresses the hyperinflammatory state of inflamed heart. The expression of IFN-γ and Spi1 also decreased. These highlighted the therapeutic potential of IVIG and IFN-γ/Spi1 axis targeted therapy. The comprehensive spatiotemporal omics analysis, conducted pre- and post-FM treatment, has offered profound insights, significantly advancing our understanding and facilitating the strategic management of FM.

3An Organ-wide Spatiotemporal Transcriptomic and Cellular Atlas of the Regenerating Zebrafish HeartSource: STOmics DB (ID: STT0000071 )

Adult zebrafish robustly regenerate injured hearts through a complex orchestration of cells and molecules. However, the comprehensive process remains incompletely understood. Here, we utilized single-cell RNA-sequencing (scRNA-seq) and Stereo-seq approaches to generate a spatially-resolved cell dataset of regenerating zebrafish heart. We captured organ-scale cellular dynamics across eight time points, with a particular focus on the initiative stages. We reconstructed a 4D "virtual regenerating heart" atlas, encompassing 3 spatial dimensions and time, comprising a total of 569,896 cells/spots derived from 36 scRNA-seq libraries and 224 Stereo-seq slices.

4Multi-omics project research on germ-free mice.Source: STOmics DB (ID: STT0000129 )

The gut microbiota influences host immunity and metabolism, and changes in its composition and function have been implicated in several non-communicable diseases. Here, comparing germ-free (GF) and specific pathogen-free (SPF) mice using spatial transcriptomics, single-cell RNA sequencing, and targeted bile acid metabolomics across multiple organs, we systematically assessed how the gut microbiota's absence affected organ morphology, immune homeostasis, bile acid, and lipid metabolism. Through integrated analysis, we detect marked aberration in B, myeloid, and T/NK cells, altered mucosal zonation and nutrient uptake, and significant shifts in bile acid profiles in feces, liver, and circulation, with the alternate synthesis pathway predominant in GF mice, and pronounced changes in bile acid enterohepatic circulation.Particularly, autophagy-driven lipid droplet breakdown in ileum epithelium and the liver's zinc finger and BTB domain containing protein (ZBTB20)- Lipoprotein lipase (LPL) axis are key to plasma lipid homeostasis in GF mice. Our results unveil the complexity of microbiota-host interactions in the crosstalk between commensal gut bacteria and the host.

5Exploring the Cellular and Molecular Basis of Murine Cardiac Development through Spatiotemporal Transcriptome SequencingSource: STOmics DB (ID: STT0000062 )

Spatial transcriptomics is a powerful tool that combines molecular data with spatial information, enabling a deeper understanding of tissue morphology and cellular interactions. In this study, we employed state-of-the-art spatial transcriptome sequencing technology to investigate the development of the mouse heart and establish a comprehensive spatiotemporal cell atlas of early murine cardiac development. Through the analysis of this atlas, we elucidated the spatial organization of cardiac cellular lineages and their interactions during development. Notably, we observed dynamic changes in gene expression within major cell lineages, including fibroblasts and cardiomyocytes. Furthermore, we identified critical genes such as IGF2, H19, and TCAP that may be associated with the loss of regeneration ability during development. Additionally, we predicted potential transcription factors, including TCF12 and Plagl1, that are likely involved in losing regeneration during early heart developing stage. Moreover, we successfully identified marker genes, such as Adamts8 and Bmp10, that can distinguish between the left and right atria. Our study provides novel insights into murine cardiac development and offers a valuable resource for future investigations in the field of heart research.

6Single cell resolved spatial immune repertoire unveils spatial heterogeneity of lymphoid aggregates in perturbed tissues[st]Source: STOmics DB (ID: STT0000123 )

T cells and B cells mediate antigen-specific inflammation. Tracing T cell and B cell clonal activity through heritable receptor sequences could provide significant insights on immune surveillance and regulation, while current available tools could not provide clonal information at single cell resolution with spatial distribution simultaneously. To break through this, we developed an ultra-sensitive T/B cell receptor sequencing strategy based on stereo-seq. Thus, we yielded a spatially resolved immune repertoire atlas at single cell resolution and observed heterogenic LAs with varied clonal activity in perturbed tissues. Specifically, 50um-2000um micro aggregates formed in a kidney cancer for T and B cell clonal expansion. Intratumoral tertiary lymphoid structure (TLS) primed significantly higher proportion of mutated B/plasma clones over peritumoral TLS in lung cancer. In inflammatory bowel disease, immigrant B/plasma cells matured in the plasma cell aggregates within the lamina propria, instead of the submucosal TLS, to mediate locoregional inflammation. Collectively, our study provides an effective approach to profile spatial immune repertoire at single cell resolution with paired TCR/BCR chains, allowing us to decipher T/B cell clonal activities crossing perturbed tissues.

7Spatially resolved multi-omics analytics of pituitary plasticity in mammalsSource: STOmics DB (ID: STT0000021 )

The plasticity of pituitary hormone production regulates the neuroendocrine adaptation of puberty, reproduction and homeostatic metabolism. However, the anatomical structures, functional cell populations and regulatory networks in the adult pituitary are still not fully elucidated. Here, we integrate omics data of the single-nucleus RNA and ATAC sequencing, high-resolution spatial transcriptomics, and metabolomics to investigate the molecular features of cell diversity and plasticity in anterior pituitaries from adult human, monkey and mouse. Our results reveal the comprehensive cell composition, novel anatomical and molecular features of hormonal cells, stromal cells, stem and progenitor cells. Analysis of differentially expressed genes along pseudotime trajectory, RNA velocity and transcription factor activity unveil the critical regulatory network for cell fate determination and functions, including Axon guidance and Hippo pathways. The importance of endoplasmic reticulum stress and unfolded protein response in the regulation of hormone production and oxidative stress is identified. Consistently, enrichment of potent antioxidants such as spermine and glutathione are detected in mouse hormonal cells. Furthermore, the putative receptor-ligand interactions reveal regulatory relationships between diverse cells, suggesting the pituitary stem cell niche comprising stromal cells expressing extracellular matrix proteins and growth factors. Our findings systematically illustrate the cellular and mechanistic basis of mammalian pituitary plasticity.

8Public Datasets of STOmicsSource: STOmics DB (ID: STT0000124 )

Browse and obtain STOmics public datasets for further exploration needs.

9Microbiota-mediated shaping of mouse spleen structure and immune function characterized by scRNA-seq and Stereo-seqSource: STOmics DB (ID: STT0000089 )

Gut microbes exhibit complex interactions with their hosts and shape an organism immune system throughout its lifespan. As the largest secondary lymphoid organ, the spleen has a wide range of immunological functions. To explore the role of microbiota in regulating and shaping the spleen, we employ scRNA-seq and Stereo-seq technologies based on germ-free (GF) mice to detect differences in tissue size, anatomical structure, cell types, functions, and spatial molecular characteristics. We identify 18 cell types, 9 subtypes of T cells, and 7 subtypes of B cells. Gene differential expression analysis reveals that the absence of microorganisms results in alterations in erythropoiesis within the red pulp region and congenital immune deficiency in the white pulp region. Stereo-seq results demonstrate a clear hierarchy of immune cells in the spleen, including marginal zone (MZ) macrophages, MZ B cells, follicular B cells and T cells, distributed in a well-defined pattern from outside to inside. However, this hierarchical structure is disturbed in GF mice. Ccr7 and Cxcl13 chemokines are specifically expressed in the spatial locations of T cells and B cells, respectively. We speculate that the microbiota may mediate the structural composition or partitioning of spleen immune cells by modulating the expression levels of chemokines.

10Fate Determination of Cancer-associated Fibroblast Drives Polarized Immunity in Cancer-stroma BoundarySource: STOmics DB (ID: STT0000036 )

The exciting responding rate to anti-PD1 treatment makes dMMR colorectal cancer (CRC) an outstanding model to explore the mechanism underlying immunotherapy sensitivity. This study provides a spatial transcriptomic landscape of CRC tumor at 50 μm resolution and highlights the plasticity of the cancer-stroma boundary immunity. It demonstrates the utility of high-resolution spatial transcriptome to study the cellular components and molecular pattern in the microscopic boundary, in which cancer cells co-opt stromal cells to alter the boundary immunity.