scholarly journals A Web Portal and Workbench for Biological Dissection of Single Cell COVID-19 Host Responses

2021 ◽  
Author(s):  
Kang Jin ◽  
Eric E Bardes ◽  
Alexis Mitelpunkt ◽  
Yunguan Jake Wang ◽  
Surbhi Bhatnagar ◽  
...  
Keyword(s):  
Single Cell ◽  
Gene Signature ◽  
Host Responses ◽  
Web Portal ◽  
Tissue Samples ◽  
Cell Recruitment ◽  
Expression Of Genes ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Cell Activator

Numerous studies have provided single-cell transcriptome profiles of host responses to SARS-CoV-2 infection. Critically lacking however is a reusable datamine to allow users to compare and explore these data for insight, inference, and hypothesis generation. To accomplish this, we harmonized datasets from blood, bronchoalveolar lavage and tissue samples from COVID-19 and other control conditions and derived a compendium of gene signature modules per cell type, subtype, clinical condition and compartment. We demonstrate approaches for exploring and evaluating their significance via a new interactive web portal (ToppCell). As examples, we develop three hypotheses: (1) a multicellular signaling cascade among alternatively differentiated monocyte-derived macrophages whose tasks include T cell recruitment and activation; (2) novel platelet subtypes with drastically modulated expression of genes responsible for adhesion, coagulation and thrombosis; (3) a multilineage cell activator network able to drive extrafollicular B maturation via an ensemble of genes extensively associated with risk for developing autoimmunity.

scholarly journals Single-cell transcriptomics identifies CD44 as a new marker and regulator of haematopoietic stem cells development

2018 ◽  
Author(s):  
Morgan Oatley ◽  
Özge Vargel Bölükbasi ◽  
Valentine Svensson ◽  
Maya Shvartsman ◽  
Kerstin Ganter ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Single Cell ◽  
Tca Cycle ◽  
Notch Signalling ◽  
Haematopoietic Stem Cells ◽  
Expression Of Genes ◽  
The Tca Cycle ◽  
Stem And Progenitor Cells ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

AbstractThe endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening we identified CD44 as a new marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta gonad mesonephros (AGM) region. This allowed us to provide a very detailed phenotypical and transcriptional profile for haemogenic endothelial cells, characterising them with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists (Smad6, Smad7 and Bmper) and a downregulation of genes related to glycolysis and the TCA cycle. Moreover, we demonstrated that by inhibiting the interaction between CD44 and its ligand hyaluronan we could block EHT, identifying a new regulator of HSPC development.

scholarly journals Longitudinal multi-omics analysis identifies responses of megakaryocytes, erythroid cells and plasmablasts as hallmarks of severe COVID-19 trajectories

2020 ◽  
Author(s):  
Joana P. Bernardes ◽  
Neha Mishra ◽  
Florian Tran ◽  
Thomas Bahmer ◽  
Lena Best ◽  
...  
Keyword(s):  
Single Cell ◽  
Severe Disease ◽  
Disease Outcome ◽  
Host Responses ◽  
Erythroid Cell ◽  
Type I ◽  
Disease Trajectory ◽  
Life Threatening ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

The pandemic spread of the potentially life-threatening disease COVID-19 requires a thorough understanding of the longitudinal dynamics of host responses. Temporal resolution of cellular features associated with a severe disease trajectory will be a pre-requisite for finding disease outcome predictors. Here, we performed a longitudinal multi-omics study using a two-centre German cohort of 13 patients (from Cologne and Kiel, cohort 1). We analysed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. The results from single-cell and bulk transcriptome analyses were validated in two independent cohorts of COVID-19 patients from Bonn (18 patients, cohort 2) and Nijmegen (40 patients, cohort 3), respectively. We observed an increase of proliferating, activated plasmablasts in severe COVID-19, and show a distinct expression pattern related to a hyperactive cellular metabolism of these cells. We further identified a notable expansion of type I IFN-activated circulating megakaryocytes and their progenitors, indicative of emergency megakaryopoiesis, which was confirmed in cohort 2. These changes were accompanied by increased erythropoiesis in the critical phase of the disease with features of hypoxic signalling. Finally, projecting megakaryocyte- and erythroid cell-derived co-expression modules to longitudinal blood transcriptome samples from cohort 3 confirmed an association of early temporal changes of these features with fatal COVID-19 disease outcome. In sum, our longitudinal multi-omics study demonstrates distinct cellular and gene expression dynamics upon SARS-CoV-2 infection, which point to metabolic shifts of circulating immune cells, and reveals changes in megakaryocytes and increased erythropoiesis as important outcome indicators in severe COVID-19 patients.

scholarly journals Enriched expression of genes associated with autism spectrum disorders in human inhibitory neurons

2017 ◽  
Author(s):  
Ping Wang ◽  
Dejian Zhao ◽  
Herbert M. Lachman ◽  
Deyou Zheng
Keyword(s):  
Single Cell ◽  
Gene Networks ◽  
Developmental Stages ◽  
Cell Types ◽  
Autism Spectrum ◽  
Inhibitory Neurons ◽  
Expression Of Genes ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Upregulated Genes

AbstractAutism spectrum disorder (ASD) is highly heritable but genetically heterogeneous. The affected neural circuits and cell types remain unclear and may vary at different developmental stages. By analyzing multiple sets of human single cell transcriptome profiles, we found that ASD candidates showed enriched gene expression in neurons, especially in inhibitory neurons. ASD candidates were also more likely to be the hubs of the co-expressed module that is highly expressed in inhibitory neurons, a feature not detected for excitatory neurons. In addition, we found that upregulated genes in multiple ASD cortex samples were also enriched with genes highly expressed in inhibitory neurons, suggesting a potential increase of inhibitory neurons and an imbalance in the ratio between excitatory and inhibitory neurons. Furthermore, the downstream targets of several ASD candidates, such as CHD8, EHMT1 and SATB2, also displayed enriched expression in inhibitory neurons. Taken together, our analysis of single cell transcriptomic data suggest that inhibitory neurons may be the major neuron subtype affected by the disruption of ASD gene networks, providing single cell functional evidence to support the excitatory/inhibitory (E/I) imbalance hypothesis.

scholarly journals Single cell transcriptome atlas of mouse mammary epithelial cells across development

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Bhupinder Pal ◽  
Yunshun Chen ◽  
Michael J. G. Milevskiy ◽  
François Vaillant ◽  
Lexie Prokopuk ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Single Cell ◽  
Developmental Stages ◽  
Mammary Epithelial Cells ◽  
Expression Profiles ◽  
Single Cells ◽  
Chromatin Accessibility ◽  
Mammary Epithelial ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome

Abstract Background Heterogeneity within the mouse mammary epithelium and potential lineage relationships have been recently explored by single-cell RNA profiling. To further understand how cellular diversity changes during mammary ontogeny, we profiled single cells from nine different developmental stages spanning late embryogenesis, early postnatal, prepuberty, adult, mid-pregnancy, late-pregnancy, and post-involution, as well as the transcriptomes of micro-dissected terminal end buds (TEBs) and subtending ducts during puberty. Methods The single cell transcriptomes of 132,599 mammary epithelial cells from 9 different developmental stages were determined on the 10x Genomics Chromium platform, and integrative analyses were performed to compare specific time points. Results The mammary rudiment at E18.5 closely aligned with the basal lineage, while prepubertal epithelial cells exhibited lineage segregation but to a less differentiated state than their adult counterparts. Comparison of micro-dissected TEBs versus ducts showed that luminal cells within TEBs harbored intermediate expression profiles. Ductal basal cells exhibited increased chromatin accessibility of luminal genes compared to their TEB counterparts suggesting that lineage-specific chromatin is established within the subtending ducts during puberty. An integrative analysis of five stages spanning the pregnancy cycle revealed distinct stage-specific profiles and the presence of cycling basal, mixed-lineage, and 'late' alveolar intermediates in pregnancy. Moreover, a number of intermediates were uncovered along the basal-luminal progenitor cell axis, suggesting a continuum of alveolar-restricted progenitor states. Conclusions This extended single cell transcriptome atlas of mouse mammary epithelial cells provides the most complete coverage for mammary epithelial cells during morphogenesis to date. Together with chromatin accessibility analysis of TEB structures, it represents a valuable framework for understanding developmental decisions within the mouse mammary gland.

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