Spatial Transcriptome Uncovers the Mouse Lung Architectures and Functions

Jiang, Yujia; Hao, Shijie; Chen, Xi; Cheng, Mengnan; Xu, Jiangshan; Li, Chenghao; Zheng, Huiwen; Volpe, Giacomo; Chen, Ao; Liao, Sha; Liu, Chuanyu; Liu, Longqi; Xu, Xun

doi:10.3389/fgene.2022.858808

Cited by 6 publications

(7 citation statements)

References 77 publications

(84 reference statements)

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“…teractions in varying resolutions. We provide a compre-299 hensive assessment of SPIDER's capacity to identify SVIs 300 on data sets from four ST sequencing technologies with vari-301 ous resolutions: the Visium PDAC dataset at a bulk resolution 302 (26), the stereo-seq mouse lung dataset almost at a single-cell 303 resolution (28), as well as the seqFISH mouse organogene-304 sis dataset (27), and the slide-seq V2 mouse brain dataset at 305 the single-cell resolution (8). For validating the quality of 306 identified SVIs, we utilize a combination of two spatial auto-307 correlation measurements and three ranking metrics used by 308 spatially variable gene (SVG) identification methods.…”

Section: Spider Identifies Spatially Variable Ligand-receptor In-298mentioning

confidence: 99%

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Finding spatially variable ligand-receptor interactions from spatial transcriptomes

WANG

LIU

et al. 2023

Preprint

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Spatial transcriptomics has emerged as a groundbreaking tool for studying ligand-receptor interactions between cells, and such interactions exhibit spatial variability. To identify spatially variable ligand-receptor interactions (SVIs), we present SPIDER, which constructs cell-cell interaction interfaces and profiles, and identifies spatially variable interaction signals with multiple probabilistic models. We applied SPIDER to six datasets from four platforms of various tissues and obtained intriguing insights. First, we found the SPIDER-constructed interaction interfaces preserving the layer structure in the human dorsolateral prefrontal cortex samples. Similarly, on a human breast cancer dataset, we found interface clusters representing cancer in situ, invasive cancer, and tumor boundaries. Subsequently, applying SPIDER on mouse lung and human pancreatic ductal adenocarcinoma samples produces SVIs that correlate with cell-type markers, annotated clusters, and deconvoluted celltypes, suggesting that SVIs could represent distinct functions from celltypes. Additionally, on a developing mouse embryo dataset, SPIDER identifies distinct SVIs marking sub-brain regions, showing the potential of SVI in representing regional interactions. Investigation into the relation between spatially variable genes and SVIs suggests that the spatial variance of SVIs does not originate from ligands and receptors and that SVI and SVG are complementary in providing biological insights as SVIs enrich additional signaling pathways.

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Section: Spider Identifies Spatially Variable Ligand-receptor In-298mentioning

confidence: 99%

“…Analysis results not included in the 783 manuscript are described in Supplementary Result 2.1. Raw data and clusters of the stereo-785 seq mouse lung samples are collected under NCBI project 786 PRJNA798781(28). Celltype deconvolution result with 787 paired scRNA-seq data of sample D2 is provided by the au-788 thors.…”

mentioning

confidence: 99%

Finding spatially variable ligand-receptor interactions from spatial transcriptomes

WANG

LIU

et al. 2023

Preprint

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“… From the neonatal side, minimally invasive exposome analyses of biosamples (e.g., cord blood, oral and laryngotracheal secretion, urine) at birth and longitudinally in the postnatal period are valuable for retrospectively analyzing prenatal events and predicting neonatal morbidities [ 142 , 143 ], yet the roles of many identified biomarkers remain to be further clarified. Cutting-edge single-cell technology and systems biology combining multiple omics will greatly contribute to the exploration and delineation of cell-specific interactions and molecular pathways underlying lung development and injury [ 38 , 113 , 144 ]. Future neonatal management concept needs to focus on a more personalized approach that accounts for perinatal exposure (e.g., microbial type, duration, and severity of IAI), GA, and multi-omic profiling.…”

Section: Conclusion and Future Clinical And Preclinical Perspectivesmentioning

confidence: 99%

“…To truly reflect clinically relevant scenarios, future research should include Gram-positive bacteria and fully consider the polymicrobial and sequential nature of IAI. Technical advances in small animal imaging [ 61 , 107 ], lineage labeling [ 122 , 127 ], and spatial multi-omics [ 144 ] potentiate the generation of integrative high-resolution atlas of lung development, homeostasis, and disease, thereby revolutionizing the search for therapeutic candidates.…”

Section: Conclusion and Future Clinical And Preclinical Perspectivesmentioning

confidence: 99%

Insights into the Black Box of Intra-Amniotic Infection and Its Impact on the Premature Lung: From Clinical and Preclinical Perspectives

Dong

Rivetti

Lingampally

et al. 2022

IJMS

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Intra-amniotic infection (IAI) is one major driver for preterm birth and has been demonstrated by clinical studies to exert both beneficial and injurious effects on the premature lung, possibly due to heterogeneity in the microbial type, timing, and severity of IAI. Due to the inaccessibility of the intra-amniotic cavity during pregnancies, preclinical animal models investigating pulmonary consequences of IAI are indispensable to elucidate the pathogenesis of bronchopulmonary dysplasia (BPD). It is postulated that on one hand imbalanced inflammation, orchestrated by lung immune cells such as macrophages, may impact on airway epithelium, vascular endothelium, and interstitial mesenchyme, resulting in abnormal lung development. On the other hand, excessive suppression of inflammation may as well cause pulmonary injury and a certain degree of inflammation is beneficial. So far, effective strategies to prevent and treat BPD are scarce. Therapeutic options targeting single mediators in signaling cascades and mesenchymal stromal cells (MSCs)-based therapies with global regulatory capacities have demonstrated efficacy in preclinical animal models and warrant further validation in patient populations. Ante-, peri- and postnatal exposome analysis and therapeutic investigations using multiple omics will fundamentally dissect the black box of IAI and its effect on the premature lung, contributing to precisely tailored and individualized therapies.

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“…The recently developed Stereo-seq, using the random barcode-labeled DNA nanosphere microarray pattern deposition, presents higher resolution and larger field-of-view than previously reported spatial transcriptomics methods. This method has recently been used to establish spatial and temporal transcriptome profiles of mouse embryos, Drosophila embryos, zebrafish embryos, axolotl brain and Arabidopsis leaves ( Chen et al, 2022a ; Cheng et al, 2022 ; Jiang et al, 2022 ; Liu et al, 2022 ; Wang et al, 2022 ; Xia et al, 2022 ). In this study, we successfully constructed the spatial transcriptome of human placental villi using a modified protocol of Stereo-seq, which provides a valuable resource for future placental researches.…”

Section: Introductionmentioning

confidence: 99%

Resolving the gene expression maps of human first-trimester chorionic villi with spatial transcriptome

Liu

Zhai

Zhang

et al. 2022

Front. Cell Dev. Biol.

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The placenta is important for fetal development in mammals, and spatial transcriptomic profiling of placenta helps to resolve its structure and function. In this study, we described the landscape of spatial transcriptome of human placental villi obtained from two pregnant women at the first trimester using the modified Stereo-seq method applied for paraformaldehyde (PFA) fixation samples. The PFA fixation of human placenta villi was better than fresh villi embedded in optimum cutting temperature (OCT) compound, since it greatly improved tissue morphology and the specificity of RNA signals. The main cell types in chorionic villi such as syncytiotrophoblasts (SCT), villous cytotrophoblasts (VCT), fibroblasts (FB), and extravillous trophoblasts (EVT) were identified with the spatial transcriptome data, whereas the minor cell types of Hofbauer cells (HB) and endothelial cells (Endo) were spatially located by deconvolution of scRNA-seq data. We demonstrated that the Stereo-seq data of human villi could be used for sophisticated analyses such as spatial cell-communication and regulatory activity. We found that the SCT and VCT exhibited the most ligand-receptor pairs that could increase differentiation of the SCT, and that the spatial localization of specific regulons in different cell types was associated with the pathways related to hormones transport and secretion, regulation of mitotic cell cycle, and nutrient transport pathway in SCT. In EVT, regulatory pathways such as the epithelial to mesenchyme transition, epithelial development and differentiation, and extracellular matrix organization were identified. Finally, viral receptors and drug transporters were identified in villi according to the pathway analysis, which could help to explain the vertical transmission of several infectious diseases and drug metabolism efficacy. Our study provides a valuable resource for further investigation of the placenta development, physiology and pathology in a spatial context.

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Spatial Transcriptome Uncovers the Mouse Lung Architectures and Functions

Abstract: We applied the Hotspot software (v0.9.1) with the chosen model parameter "normal" to detect spatially variable genes (DeTomaso and Yosef, 2021). First, the variable genes were grouped into

Cited by 6 publications

References 77 publications

Finding spatially variable ligand-receptor interactions from spatial transcriptomes

Finding spatially variable ligand-receptor interactions from spatial transcriptomes

Insights into the Black Box of Intra-Amniotic Infection and Its Impact on the Premature Lung: From Clinical and Preclinical Perspectives

Resolving the gene expression maps of human first-trimester chorionic villi with spatial transcriptome

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