scholarly journals Single-cell transcriptomes identify human islet cell signatures and reveal cell-type–specific expression changes in type 2 diabetes

2016 ◽  
Vol 27 (2) ◽  
pp. 208-222 ◽  
Author(s):  
Nathan Lawlor ◽  
Joshy George ◽  
Mohan Bolisetty ◽  
Romy Kursawe ◽  
Lili Sun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Single Cell ◽  
Islet Cell ◽  
Human Islet ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Abstract WP292: Insulin Resistance is Associated with a Reduction of Leukocyte Surface CD36 Expression and an Increase of Soluble CD36

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Atsushi Kanoke ◽  
Yasuo Nishijima ◽  
Christine L Hsieh ◽  
Jialing Liu
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Plasma Level ◽  
Surface Expression ◽  
Oral Glucose ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Introduction: Diabetes is a major risk factor for ischemic stroke. Evidence suggests that the deficiency in CD36 is linked to insulin resistance in humans, yet patients with type 2 diabetes often display elevated plasma level of soluble CD36 (sCD36). However, cell type specific expression of CD36 is not well understood in the context of type 2 diabetes. Hypothesis: We hypothesize that insulin resistance is correlated with a reduction in the surface expression of CD36 among inflammatory cells, coincident with an increase in sCD36. Methods: Middle-aged db/db and db/+ mice (30-50 weeks-old) were subjected to left distal middle cerebral artery occlusion (dMCAO) or sham surgery. One, 3, or 7 days after stroke, leukocytes from blood and left hemisphere of the brain were analyzed by flow cytometry for cell type specific expression of CD36. The level of sCD36 in platelet free plasma was determined by ELISA. PPAR-γ agonist pioglitazone was administered at 2.5 mg/kg/day by oral gavage. Oral glucose tolerance test was performed at baseline and following two weeks of drug treatment. Both form of CD36 was also measured in 3-week-old mice without stroke. Results: Infiltrating neutrophils in brain peaked at 1 day after dMCAO, in contrast to a delayed but sustained increase of macrophages from 3 to 7 days post stroke. The adult db/db mice had a lower leukocyte surface expression of CD36 in both blood and brain, but had a higher level of sCD36 compared to age-matched db/+ mice whether at baseline or after stroke. The sCD36 is unlikely to exist in the form of extracellular vesicles (EV) since there were very few CD36(+) EVs detected in either type of mice. Prior to the development of obesity, 3-week-old db/db mice had similar leukocyte CD36 surface expression and plasma level of sCD36 compared to juvenile db/+ mice. Pioglitazone improved glucose sensitivity and enhanced macrophage CD36 surface expression in db/db mice after stroke. Conclusions: The reduced surface expression of CD36 on leukocytes and increased sCD36 was directly correlated with insulin resistance. Ongoing studies will determine the molecular event induced by obesity that triggers the cleavage of CD36 and how it affects macrophage function in the setting of diabetes.

scholarly journals Dynamics of gene expression in single root cells ofA. thaliana

2018 ◽  
Author(s):  
Ken Jean-Baptiste ◽  
José L. McFaline-Figueroa ◽  
Cristina M. Alexandre ◽  
Michael W. Dorrity ◽  
Lauren Saunders ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Developmental Trajectories ◽  
Cell Types ◽  
Cell Type ◽  
Specific Expression ◽  
Root Cells ◽  
Cell Lineages ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTSingle-cell RNA-seq can yield high-resolution cell-type-specific expression signatures that reveal new cell types and the developmental trajectories of cell lineages. Here, we apply this approach toA. thalianaroot cells to capture gene expression in 3,121 root cells. We analyze these data with Monocle 3, which orders single cell transcriptomes in an unsupervised manner and uses machine learning to reconstruct single-cell developmental trajectories along pseudotime. We identify hundreds of genes with cell-type-specific expression, with pseudotime analysis of several cell lineages revealing both known and novel genes that are expressed along a developmental trajectory. We identify transcription factor motifs that are enriched in early and late cells, together with the corresponding candidate transcription factors that likely drive the observed expression patterns. We assess and interpret changes in total RNA expression along developmental trajectories and show that trajectory branch points mark developmental decisions. Finally, by applying heat stress to whole seedlings, we address the longstanding question of possible heterogeneity among cell types in the response to an abiotic stress. Although the response of canonical heat shock genes dominates expression across cell types, subtle but significant differences in other genes can be detected among cell types. Taken together, our results demonstrate that single-cell transcriptomics holds promise for studying plant development and plant physiology with unprecedented resolution.

scholarly journals O4-10-01: CHARACTERIZING CELL TYPE-SPECIFIC EXPRESSION SIGNATURES IN BRAIN USING SINGLE CELL RNA SEQUENCING

2019 ◽  
Vol 15 ◽  
pp. P1258-P1258 ◽  
Author(s):  
Tulsi Patel ◽  
Troy Carnwath ◽  
Laura Lewis-Tuffin ◽  
Mariet Allen ◽  
Sarah J. Lincoln ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Cell Type ◽  
Specific Expression ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

scholarly journals Single-Cell Regulatory Network Inference and Clustering Identifies Cell-Type Specific Expression Pattern of Transcription Factors in Mouse Sciatic Nerve

2021 ◽  
Vol 15 ◽  
Author(s):  
Mingchao Li ◽  
Qing Min ◽  
Matthew C. Banton ◽  
Xinpeng Dun
Keyword(s):  
Transcription Factors ◽  
Sciatic Nerve ◽  
Single Cell ◽  
Cell Types ◽  
Cell Type ◽  
Specific Expression ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Different Cell Types

Advances in single-cell RNA sequencing technologies and bioinformatics methods allow for both the identification of cell types in a complex tissue and the large-scale gene expression profiling of various cell types in a mixture. In this report, we analyzed a single-cell RNA sequencing (scRNA-seq) dataset for the intact adult mouse sciatic nerve and examined cell-type specific transcription factor expression and activity during peripheral nerve homeostasis. In total, we identified 238 transcription factors expressed in nine different cell types of intact mouse sciatic nerve. Vascular smooth muscle cells have the lowest number of transcription factors expressed with 17 transcription factors identified. Myelinating Schwann cells (mSCs) have the highest number of transcription factors expressed, with 61 transcription factors identified. We created a cell-type specific expression map for the identified 238 transcription factors. Our results not only provide valuable information about the expression pattern of transcription factors in different cell types of adult peripheral nerves but also facilitate future studies to understand the function of key transcription factors in the peripheral nerve homeostasis and disease.

scholarly journals Single-Cell mRNA Profiling Reveals Cell-Type-Specific Expression of Neurexin Isoforms

Neuron ◽  
2015 ◽  
Vol 87 (2) ◽  
pp. 326-340 ◽  
Author(s):  
Marc V. Fuccillo ◽  
Csaba Földy ◽  
Özgün Gökce ◽  
Patrick E. Rothwell ◽  
Gordon L. Sun ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Type ◽  
Specific Expression ◽  
Mrna Profiling ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

scholarly journals Pathogenesis Study Based on High Throughput Single-Cell Sequencing Analysis Reveals Novel Transcriptional Landscape and Heterogeneity of Retinal Cells in Type 2 Diabetic Mice

2021 ◽  
Author(s):  
Tian Niu ◽  
Junwei Fang ◽  
Xin Shi ◽  
Mengya Zhao ◽  
Xindan Xing ◽  
...  
Keyword(s):  
Single Cell ◽  
Leptin Receptor ◽  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
Sequencing Analysis ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific ◽  
Type 2 Diabetic

<a>Diabetic retinopathy (DR) is the leading cause of acquired blindness in middle-aged people. The complex pathology of DR is difficult to dissect, given the convoluted cytoarchitecture of the retina. Here, we performed single-cell RNA sequencing (scRNA-seq) of retina from type 2 diabetic model induced in leptin receptor-deficient (db/db) and control db/m mice with the aim of elucidating the factors mediating the pathogenesis of DR. We </a><a></a><a>identified eleven cell types</a> and <a></a><a>determined </a>cell type-specific expression of DR-associated loci via genome-wide association study-based enrichment analysis. DR also impacted cell type-specific genes and altered cell-cell communication. Based on the scRNA-seq results, retinaldehyde-binding protein 1 (RLBP1) was investigated as a promising therapeutic target for DR. Retinal RLBP1 expression was decreased in diabetes, and its overexpression in Müller glia mitigated DR-associated neurovascular degeneration. These data provide a detailed analysis of the retina under diabetic and normal conditions, revealing new insights into pathogenic factors that may be targeted to treat DR and related dysfunctions.

scholarly journals Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

2020 ◽  
Author(s):  
Christoph Muus ◽  
Malte D. Luecken ◽  
Gokcen Eraslan ◽  
Avinash Waghray ◽  
Graham Heimberg ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Single Cell ◽  
Viral Entry ◽  
Integrated Analysis ◽  
Target Cells ◽  
Specific Cell ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTThe COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis.

scholarly journals Pathogenesis Study Based on High Throughput Single-Cell Sequencing Analysis Reveals Novel Transcriptional Landscape and Heterogeneity of Retinal Cells in Type 2 Diabetic Mice

2021 ◽  
Author(s):  
Tian Niu ◽  
Junwei Fang ◽  
Xin Shi ◽  
Mengya Zhao ◽  
Xindan Xing ◽  
...  
Keyword(s):  
Single Cell ◽  
Leptin Receptor ◽  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
Sequencing Analysis ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific ◽  
Type 2 Diabetic

<a>Diabetic retinopathy (DR) is the leading cause of acquired blindness in middle-aged people. The complex pathology of DR is difficult to dissect, given the convoluted cytoarchitecture of the retina. Here, we performed single-cell RNA sequencing (scRNA-seq) of retina from type 2 diabetic model induced in leptin receptor-deficient (db/db) and control db/m mice with the aim of elucidating the factors mediating the pathogenesis of DR. We </a><a></a><a>identified eleven cell types</a> and <a></a><a>determined </a>cell type-specific expression of DR-associated loci via genome-wide association study-based enrichment analysis. DR also impacted cell type-specific genes and altered cell-cell communication. Based on the scRNA-seq results, retinaldehyde-binding protein 1 (RLBP1) was investigated as a promising therapeutic target for DR. Retinal RLBP1 expression was decreased in diabetes, and its overexpression in Müller glia mitigated DR-associated neurovascular degeneration. These data provide a detailed analysis of the retina under diabetic and normal conditions, revealing new insights into pathogenic factors that may be targeted to treat DR and related dysfunctions.

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