scholarly journals Single cell atlas for 11 non-model mammals, reptiles and birds

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dongsheng Chen ◽  
Jian Sun ◽  
Jiacheng Zhu ◽  
Xiangning Ding ◽  
Tianming Lan ◽  
...  
Keyword(s):  
Single Cell ◽  
Viral Entry ◽  
Large Scale ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Target Cells ◽  
Animal Cells ◽  
Regulatory Circuits ◽  
Single Nucleus

AbstractThe availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.

scholarly journals Discovering Distinct Patterns in Gene Expression Profiles

2008 ◽  
Vol 5 (2) ◽  
Author(s):  
Li Teng ◽  
Laiwan Chan
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Clustering Methods ◽  
Gene Expressions ◽  
Real Gene ◽  
Large Scale Dataset ◽  
Coexpressed Genes

SummaryTraditional analysis of gene expression profiles use clustering to find groups of coexpressed genes which have similar expression patterns. However clustering is time consuming and could be diffcult for very large scale dataset. We proposed the idea of Discovering Distinct Patterns (DDP) in gene expression profiles. Since patterns showing by the gene expressions reveal their regulate mechanisms. It is significant to find all different patterns existing in the dataset when there is little prior knowledge. It is also a helpful start before taking on further analysis. We propose an algorithm for DDP by iteratively picking out pairs of gene expression patterns which have the largest dissimilarities. This method can also be used as preprocessing to initialize centers for clustering methods, like K-means. Experiments on both synthetic dataset and real gene expression datasets show our method is very effective in finding distinct patterns which have gene functional significance and is also effcient.

CFTR ΔF508 mutation has minimal effect on the gene expression profile of differentiated human airway epithelia

2005 ◽  
Vol 289 (4) ◽  
pp. L545-L553 ◽  
Author(s):  
Joseph Zabner ◽  
Todd E. Scheetz ◽  
Hakeem G. Almabrazi ◽  
Thomas L. Casavant ◽  
Jian Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Large Scale ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Primary Cultures ◽  
Gene Expression Profiles ◽  
Filter Method ◽  
Tissue Destruction ◽  
Airway Epithelia

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), an epithelial chloride channel regulated by phosphorylation. Most of the disease-associated morbidity is the consequence of chronic lung infection with progressive tissue destruction. As an approach to investigate the cellular effects of CFTR mutations, we used large-scale microarray hybridization to contrast the gene expression profiles of well-differentiated primary cultures of human CF and non-CF airway epithelia grown under resting culture conditions. We surveyed the expression profiles for 10 non-CF and 10 ΔF508 homozygote samples. Of the 22,283 genes represented on the Affymetrix U133A GeneChip, we found evidence of significant changes in expression in 24 genes by two-sample t-test ( P < 0.00001). A second, three-filter method of comparative analysis found no significant differences between the groups. The levels of CFTR mRNA were comparable in both groups. There were no significant differences in the gene expression patterns between male and female CF specimens. There were 18 genes with significant increases and 6 genes with decreases in CF relative to non-CF samples. Although the function of many of the differentially expressed genes is unknown, one transcript that was elevated in CF, the KCl cotransporter (KCC4), is a candidate for further study. Overall, the results indicate that CFTR dysfunction has little direct impact on airway epithelial gene expression in samples grown under these conditions.

Sex differences in viral entry protein expression and host transcript responses to SARS-CoV-2

2020 ◽  
Author(s):  
Mengying Sun ◽  
Rama Shankar ◽  
Meehyun Ko ◽  
Christopher Daniel Chang ◽  
Shan-Ju Yeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Viral Entry ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Scale Analysis ◽  
Transcriptional Responses ◽  
Deconvolution Analysis ◽  
Large Scale Analysis

Abstract Epidemiological studies suggest that men exhibit a higher mortality rate to COVID-19 than women, yet the underlying biology is largely unknown. Here, we seek to delineate sex differences in the gene expression of viral entry proteins ACE2 and TMPRSS2, and host transcriptional responses to SARS-CoV-2 through large-scale analysis of genomic and clinical data. We first compiled 220,000 human gene expression profiles from three databases and completed the meta-information through machine learning and manual annotation. Large scale analysis of these profiles indicated that male samples show higher expression levels of ACE2 and TMPRSS2 than female samples, especially in the older group (>60 years) and in the kidney. Subsequent analysis of 6,031 COVID-19 patients at Mount Sinai Health System revealed that men have significantly higher creatinine levels, an indicator of impaired kidney function. Further analysis of 782 COVID-19 patient gene expression profiles taken from upper airway and blood suggested men and women present distinct expression changes. Computational deconvolution analysis of these profiles revealed male COVID-19 patients have enriched kidney-specific mesangial cells in blood compared to healthy patients. Together, this study suggests biological differences in the kidney between sexes may contribute to sex disparity in COVID-19.

scholarly journals Cells of the adult human heart

Nature ◽  
2020 ◽  
Vol 588 (7838) ◽  
pp. 466-472 ◽  
Author(s):  
Monika Litviňuková ◽  
Carlos Talavera-López ◽  
Henrike Maatz ◽  
Daniel Reichart ◽  
Catherine L. Worth ◽  
...  
Keyword(s):  
Human Heart ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cardiac Cells ◽  
Cellular Heterogeneity ◽  
Molecular Processes ◽  
Future Studies ◽  
Disease Mechanisms ◽  
Single Nucleus

AbstractCardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and therapeutic strategies require a deeper understanding of the molecular processes involved in the healthy heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavour. Here, using state-of-the-art analyses of large-scale single-cell and single-nucleus transcriptomes, we characterize six anatomical adult heart regions. Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, and reveal distinct atrial and ventricular subsets of cells with diverse developmental origins and specialized properties. We define the complexity of the cardiac vasculature and its changes along the arterio-venous axis. In the immune compartment, we identify cardiac-resident macrophages with inflammatory and protective transcriptional signatures. Furthermore, analyses of cell-to-cell interactions highlight different networks of macrophages, fibroblasts and cardiomyocytes between atria and ventricles that are distinct from those of skeletal muscle. Our human cardiac cell atlas improves our understanding of the human heart and provides a valuable reference for future studies.

scholarly journals A map of tumor–host interactions in glioma at single-cell resolution

GigaScience ◽  
2020 ◽  
Vol 9 (10) ◽  
Author(s):  
Francesca Pia Caruso ◽  
Luciano Garofano ◽  
Fulvio D'Angelo ◽  
Kai Yu ◽  
Fuchou Tang ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Cross Talk ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Sequencing Data ◽  
Host Interaction ◽  
Receptor Interactions ◽  
Single Cell Rna Sequencing

ABSTRACT Background Single-cell RNA sequencing is the reference technique for characterizing the heterogeneity of the tumor microenvironment. The composition of the various cell types making up the microenvironment can significantly affect the way in which the immune system activates cancer rejection mechanisms. Understanding the cross-talk signals between immune cells and cancer cells is of fundamental importance for the identification of immuno-oncology therapeutic targets. Results We present a novel method, single-cell Tumor–Host Interaction tool (scTHI), to identify significantly activated ligand–receptor interactions across clusters of cells from single-cell RNA sequencing data. We apply our approach to uncover the ligand–receptor interactions in glioma using 6 publicly available human glioma datasets encompassing 57,060 gene expression profiles from 71 patients. By leveraging this large-scale collection we show that unexpected cross-talk partners are highly conserved across different datasets in the majority of the tumor samples. This suggests that shared cross-talk mechanisms exist in glioma. Conclusions Our results provide a complete map of the active tumor–host interaction pairs in glioma that can be therapeutically exploited to reduce the immunosuppressive action of the microenvironment in brain tumor.

scholarly journals Revisit the Cellular Transmission and Emerging Techniques in Understanding the Mechanisms of Proteinopathies

2021 ◽  
Vol 15 ◽  
Author(s):  
Jinwen Jiang ◽  
Yu Liu ◽  
Qihui Wu
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Single Cell ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Molecular Taxonomy ◽  
Gene Expression Profiles ◽  
Underlying Mechanism ◽  
Signal Pathways ◽  
Parkinson’S Diseases

Alzheimer’s and Parkinson’s diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aβ) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aβ and α-synuclein in mediating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.

scholarly journals Single-nucleus RNA-seq identifies Huntington disease astrocyte states

2019 ◽  
Author(s):  
Osama Al-Dalahmah ◽  
Alexander A Sosunov ◽  
A Shaik ◽  
Kenneth Ofori ◽  
Yang Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Huntington Disease ◽  
Expression Profiles ◽  
Lipid Synthesis ◽  
Gene Expression Profiles ◽  
Cag Repeats ◽  
Cell Gene Expression ◽  
Single Nucleus ◽  
Cell Gene

AbstractHuntington Disease (HD) is an inherited movement disorder caused by expanded CAG repeats in the Huntingtin gene. We have used single nucleus RNASeq (snRNASeq) to uncover cellular phenotypes that change in the disease, investigating single cell gene expression in cingulate cortex of patients with HD and comparing the gene expression to that of patients with no neurological disease. In this study, we focused on astrocytes, although we found significant gene expression differences in neurons, oligodendrocytes, and microglia as well. In particular, the gene expression profiles of astrocytes in HD showed multiple signatures, varying in phenotype from cells that had markedly upregulated metallothionein and heat shock genes, but had not completely lost the expression of genes associated with normal protoplasmic astrocytes, to astrocytes that had substantially upregulated GFAP and had lost expression of many normal protoplasmic astrocyte genes as well as metallothionein genes. When compared to astrocytes in control samples, astrocyte signatures in HD also showed downregulated expression of a number of genes, including several associated with protoplasmic astrocyte function and lipid synthesis. Thus, HD astrocytes appeared in variable transcriptional phenotypes, and could be divided into several different “states”, defined by patterns of gene expression. Ultimately, this study begins to fill the knowledge gap of single cell gene expression in HD and provide a more detailed understanding of the variation in changes in gene expression during astrocyte “reactions” to the disease.

scholarly journals A survey of the mouse hindbrain in the fed and fasted state using single-nucleus RNA sequencing

2021 ◽  
Author(s):  
Georgina K.C. Dowsett ◽  
Brian Y.H. Lam ◽  
John Tadross ◽  
Irene Cimino ◽  
Debra Rimmington ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Rna Sequencing ◽  
Area Postrema ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Fasted State ◽  
Single Nucleus ◽  
Human Use ◽  
Obesity Drugs

AbstractObjectiveThe area postrema (AP) and the nucleus tractus solitaris (NTS), located in the hindbrain, are key nuclei that sense and integrate peripheral nutritional signals and, consequently, regulate feeding behaviour. While single cell transcriptomics have been used in mice to reveal the gene expression profile and heterogeneity of key hypothalamic populations, similar in-depth studies have not yet been performed in the hindbrain.MethodsUsing single-nucleus RNA sequencing, we provide a detailed survey of 16,034 cells within the AP and NTS of the mouse, in the fed and fasted state.ResultsOf these, 8910 are neurons that group into 30 clusters, with 4289 coming from mice fedad libitumand 4621 from overnight fasted mice. 7124 nuclei are from non-neuronal cells, including oligodendrocytes, astrocytes and microglia. Interestingly, we identified that the oligodendrocyte population was particularly transcriptionally sensitive to an overnight fast. The receptors GLP1R, GIPR, GFRAL and CALCR, which bind GLP1, GIP, GDF15 and amylin respectively, are all expressed in the hindbrain and are major targets for anti-obesity therapeutics. We characterise the transcriptomes of these four populations and show that their gene expression profiles are not dramatically altered by an overnight fast. Notably, we find that roughly half of cells that express GIPR are oligodendrocytes. Additionally, we profile POMC expressing neurons within the hindbrain and demonstrate that 84% of POMC neurons express either PCSK1, PSCK2 or both, implying that melanocortin peptides are likely produced by these neurons.ConclusionWe provide a detailed single-cell level characterisation of AP and NTS cells expressing receptors for key anti-obesity drugs that are either already approved for human use or are in clinical trials. This resource will help delineate the mechanisms underlying the effectiveness of these compounds, and also prove useful in the continued search for other novel therapeutic targets.

Human cord blood CD34+Pax-5+ B-cell progenitors: single-cell analyses of their gene expression profiles

Blood ◽  
2003 ◽  
Vol 101 (9) ◽  
pp. 3424-3430 ◽  
Author(s):  
Eva Sanz ◽  
Melchor Alvarez-Mon ◽  
Carlos Martı́nez-A ◽  
Antonio de la Hera
Keyword(s):  
Gene Expression ◽  
Cord Blood ◽  
B Cell ◽  
Single Cell ◽  
Developmental Stages ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Human Cord Blood

Circulating CD34+ cells are used in reparative medicine as a stem cell source, but they contain cells already committed to different lineages. Many think that B-cell progenitors (BCPs) are confined to bone marrow (BM) niches until they differentiate into B cells and that they do not circulate in blood. The prevailing convention is that BCP transit a CD34+CD19−10+early-B→CD34+CD19+CD10+B-cell progenitor (pro-B)→CD34−CD19+CD10+ B-cell precursor (pre-B) differentiation pathway within BM. However, populations of CD34+CD10+ and CD34+CD19+ cells circulate in adult peripheral blood and neonatal umbilical cord blood (CB) that are operationally taken as BCPs on the basis of their phenotypes, although they have not been submitted to a systematic characterization of their gene expression profiles. Here, conventional CD34+CD19+CD10+ and novel CD34+CD19+CD10− BCP populations are characterized in CB by single-cell sorting and multiplex analyses of gene expression patterns. Circulating BCP are Pax-5+cells that span the early-B, pro-B, and pre-B developmental stages, defined by the profiles of rearranged V-D-JH, CD79, VpreB, recombination activating gene (RAG), and terminal deoxynucleotidyl transferase (TdT) expression. Contrary to the expectation, circulating CD34+CD19−CD10+ cells are essentially devoid of Pax-5+ BCP. Interestingly, the novel CD34+CD19+CD10− BCP appears to be the normal counterpart of circulating preleukemic BCPs that undergo chromosomal translocations in utero months or years before their promotion into infant acute lymphoblastic B-cell leukemia after secondary postnatal mutations. The results underscore the power of single-cell analyses to characterize the gene expression profiles in a minor population of rare cells, which has broad implications in biomedicine.

scholarly journals Massive single-cell RNA-seq analysis and imputation via deep learning

2018 ◽  
Author(s):  
Yue Deng ◽  
Feng Bao ◽  
Qionghai Dai ◽  
Lani F. Wu ◽  
Steven J. Altschuler
Keyword(s):  
Deep Learning ◽  
Single Cell ◽  
Large Scale ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Rna Seq ◽  
Fine Grained ◽  
Cell Type Composition ◽  
Type Composition ◽  
Cell Gene Expression

Recent advances in large-scale single cell RNA-seq enable fine-grained characterization of phenotypically distinct cellular states within heterogeneous tissues. We present scScope, a scalable deep-learning based approach that can accurately and rapidly identify cell-type composition from millions of noisy single-cell gene-expression profiles.

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