Abstract:Non-human primates are attractive laboratory animal models that accurately reflect both developmental and pathological features of humans. Here we present a compendium of cell types across multiple organs in cynomolgus monkeys (Macaca fascicularis) using both single-cell chromatin accessibility and RNA sequencing data. The integrated cell map enables in-depth dissection and comparison of molecular dynamics, cell-type compositions and cellular heterogeneity across multiple tissues and organs. Using single-cell … Show more
“…To better understand the mechanism of asthma development, there is an urgent need for research on highly homogeneous animal models of human asthma ( 28 ). Given the difficulties of harvesting untreated clinical asthma samples and other issues, cynomolgus monkeys can be a reliable model for studying asthma and related conditions ( 29 – 31 ). Principally, monkeys share genetic, anatomical, and physiological similarities with humans ( 32 ), as well as a susceptibility to asthma.…”
Monkey disease models, which are comparable to humans in terms of genetic, anatomical, and physiological characteristics, are important for understanding disease mechanisms and evaluating the efficiency of biological treatments. Here, we established an A.suum-induced model of asthma in cynomolgus monkeys to profile airway inflammation and remodeling in the lungs by single-cell RNA sequencing (scRNA-seq). The asthma model results in airway hyperresponsiveness and remodeling, demonstrated by pulmonary function test and histological characterization. scRNA-seq reveals that the model elevates the numbers of stromal, epithelial and mesenchymal cells (MCs). Particularly, the model increases the numbers of endothelial cells (ECs), fibroblasts (Fibs) and smooth muscle cells (SMCs) in the lungs, with upregulated gene expression associated with cell functions enriched in cell migration and angiogenesis in ECs and Fibs, and VEGF-driven cell proliferation, apoptotic process and complement activation in SMCs. Interestingly, we discover a novel Fib subtype that mediates type I inflammation in the asthmatic lungs. Moreover, MCs in the asthmatic lungs are found to regulate airway remodeling and immunological responses, with elevated gene expression enriched in cell migration, proliferation, angiogenesis and innate immunological responses. Not only the numbers of epithelial cells in the asthmatic lungs change at the time of lung tissue collection, but also their gene expressions are significantly altered, with an enrichment in the biological processes of IL-17 signaling pathway and apoptosis in the majority of subtypes of epithelial cells. Moreover, the ubiquitin process and DNA repair are more prevalent in ciliated epithelial cells. Last, cell-to-cell interaction analysis reveals a complex network among stromal cells, MCs and macrophages that contribute to the development of asthma and airway remodeling. Our findings provide a critical resource for understanding the principle underlying airway remodeling and inflammation in a monkey model of asthma, as well as valuable hints for the future treatment of asthma, especially the airway remodeling-characterized refractory asthma.
“…To better understand the mechanism of asthma development, there is an urgent need for research on highly homogeneous animal models of human asthma ( 28 ). Given the difficulties of harvesting untreated clinical asthma samples and other issues, cynomolgus monkeys can be a reliable model for studying asthma and related conditions ( 29 – 31 ). Principally, monkeys share genetic, anatomical, and physiological similarities with humans ( 32 ), as well as a susceptibility to asthma.…”
Monkey disease models, which are comparable to humans in terms of genetic, anatomical, and physiological characteristics, are important for understanding disease mechanisms and evaluating the efficiency of biological treatments. Here, we established an A.suum-induced model of asthma in cynomolgus monkeys to profile airway inflammation and remodeling in the lungs by single-cell RNA sequencing (scRNA-seq). The asthma model results in airway hyperresponsiveness and remodeling, demonstrated by pulmonary function test and histological characterization. scRNA-seq reveals that the model elevates the numbers of stromal, epithelial and mesenchymal cells (MCs). Particularly, the model increases the numbers of endothelial cells (ECs), fibroblasts (Fibs) and smooth muscle cells (SMCs) in the lungs, with upregulated gene expression associated with cell functions enriched in cell migration and angiogenesis in ECs and Fibs, and VEGF-driven cell proliferation, apoptotic process and complement activation in SMCs. Interestingly, we discover a novel Fib subtype that mediates type I inflammation in the asthmatic lungs. Moreover, MCs in the asthmatic lungs are found to regulate airway remodeling and immunological responses, with elevated gene expression enriched in cell migration, proliferation, angiogenesis and innate immunological responses. Not only the numbers of epithelial cells in the asthmatic lungs change at the time of lung tissue collection, but also their gene expressions are significantly altered, with an enrichment in the biological processes of IL-17 signaling pathway and apoptosis in the majority of subtypes of epithelial cells. Moreover, the ubiquitin process and DNA repair are more prevalent in ciliated epithelial cells. Last, cell-to-cell interaction analysis reveals a complex network among stromal cells, MCs and macrophages that contribute to the development of asthma and airway remodeling. Our findings provide a critical resource for understanding the principle underlying airway remodeling and inflammation in a monkey model of asthma, as well as valuable hints for the future treatment of asthma, especially the airway remodeling-characterized refractory asthma.
“…Recently, empowered by the burst of single-cell sequencing techniques, references of single cell atlas across tissues or of the whole organisms have largely been generated in various model species especially in mammalian species (Qu et al, 2022;Han et al, 2020Han et al, , 2018Jones et al, 2022). To this end, the Human Cell Atlas (HCA) project aims to provide comprehensive reference maps of all human cells (Regev et al, 2017;Rozenblatt-Rosen et al, 2017).…”
Plant morphogenesis relies on precise gene expression programs at the proper time and position which is orchestrated by transcription factors (TFs) in intricate regulatory networks at a cell-type specific manner. Here we presented a reference single-cell transcriptomic atlas of Arabidopsis seedlings by integration of 40 published scRNA-seq datasets from representative tissues as well as the entire under- and above-ground parts. We identified 34 distinct cell types or states, largely expanding our current view of plant cell compositions. We then mapped the developmental trajectory of root-shoot lineage separation and identified differential gene expression programs that may regulate the cell fate determination of under- and above-ground organs. Lastly, we systematically constructed cell-type specific gene regulatory networks and uncovered key regulators that act in a coordination manner to control cell-type specific gene expression. Taken together, our study not only offers a valuable resource plant cell atlas exploration but also provides molecular insights into gene-regulatory programs that determines organ specify, particularly the differentiation between root and shoot.
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