scholarly journals A limited set of transcriptional programs define major cell types

2019 ◽  
Author(s):  
Alessandra Breschi ◽  
Manuel Muñoz-Aguirre ◽  
Valentin Wucher ◽  
Carrie A. Davis ◽  
Diego Garrido-Martín ◽  
...  
Keyword(s):  
Human Body ◽  
Blood Cells ◽  
Cell Types ◽  
Human Tissues ◽  
Primary Cells ◽  
Cellular Composition ◽  
Sequencing Data ◽  
Morphological Heterogeneity ◽  
Different Tissues ◽  
Age And Sex

AbstractWe have produced RNA sequencing data for a number of primary cells from different locations in the human body. The clustering of these primary cells reveals that most cells in the human body share a few broad transcriptional programs, which define five major cell types: epithelial, endothelial, mesenchymal, neural and blood cells. These act as basic components of many tissues and organs. Based on gene expression, these cell types redefine the basic histological types by which tissues have been traditionally classified. We identified genes whose expression is specific to these cell types, and from these genes, we estimated the contribution of the major cell types to the composition of human tissues. We found this cellular composition to be a characteristic signature of tissues, and to reflect tissue morphological heterogeneity and histology. We identified changes in cellular composition in different tissues associated with age and sex and found that departures from the normal cellular composition correlate with histological phenotypes associated to disease.One Sentence SummaryA few broad transcriptional programs define the major cell types underlying the histology of human tissues and organs.

scholarly journals On-the-fly selection of cell-specific enhancers, genes, miRNAs and proteins across the human body using SlideBase

Database ◽  
2016 ◽  
Vol 2016 ◽  
Author(s):  
Hans Ienasescu ◽  
Kang Li ◽  
Robin Andersson ◽  
Morana Vitezic ◽  
Sarah Rennie ◽  
...  
Keyword(s):  
Human Body ◽  
Individual Cell ◽  
Cell Types ◽  
Large Datasets ◽  
Human Tissues ◽  
Web Tool ◽  
Expression Of Genes ◽  
Micro Rnas ◽  
Human Protein Atlas ◽  
Selection Of

Genomics consortia have produced large datasets profiling the expression of genes, micro-RNAs, enhancers and more across human tissues or cells. There is a need for intuitive tools to select subsets of such data that is the most relevant for specific studies. To this end, we present SlideBase, a web tool which offers a new way of selecting genes, promoters, enhancers and microRNAs that are preferentially expressed/used in a specified set of cells/tissues, based on the use of interactive sliders. With the help of sliders, SlideBase enables users to define custom expression thresholds for individual cell types/tissues, producing sets of genes, enhancers etc. which satisfy these constraints. Changes in slider settings result in simultaneous changes in the selected sets, updated in real time. SlideBase is linked to major databases from genomics consortia, including FANTOM, GTEx, The Human Protein Atlas and BioGPS. Database URL: http://slidebase.binf.ku.dk

Cholinesterase activity and the innervation of peripheral tissues

1950 ◽  
Vol 137 (888) ◽  
pp. 311-320 ◽  
Keyword(s):  
Blood Cells ◽  
Animal Species ◽  
Species Differences ◽  
Cholinesterase Activity ◽  
Human Tissues ◽  
Peripheral Tissues ◽  
Initial Information ◽  
Hydrolysis Of ◽  
Comparative Information ◽  
Different Tissues

Although the nature of the cholinesterases in brain, red blood cells and plasma has been studied extensively, little comparative information is available on the distribution and characteristics of the types of cholinesterase present in other issues, and I would like to describe very briefly some of the results which Miss M. G. Ord and I have been obtaining in the course of a survey of different mammalian issues (Ord & Thompson 1950 a ). Owing to the species differences in blood esterases we have limited our work to a study of rat and human tissues. In order to obtain some initial information about the distribution of the so-called ‘true’ and ‘pseudo-’ cholinesterases we began by comparing the relative rates of hydrolysis of acetylcholine (ACh) and of acetyl- β -methylcholine (MCh) and benzoylcholine (BCh); that is to say, we used the physiological substrate and also the selective substrates for the true and pseudo-cholinesterases introduced by Mendel, Mundell & Rudney (1943). Apart from a few scattered observations on a small number of tissues from different animal species no attempt to compare systematically the distribution of these esterases in different tissues of animals of the same species was made until Sawye & Everett (1947) showed that the liver, the uterus and a number of glandula tissues of the rat were able to hydrolyze benzoylcholine more rapidly than acetyl β -methylcholine.

scholarly journals Incomplete annotation has a disproportionate impact on our understanding of Mendelian and complex neurogenetic disorders

2020 ◽  
Vol 6 (24) ◽  
pp. eaay8299 ◽  
Author(s):  
David Zhang ◽  
Sebastian Guelfi ◽  
Sonia Garcia-Ruiz ◽  
Beatrice Costa ◽  
Regina H. Reynolds ◽  
...  
Keyword(s):  
Human Gene ◽  
Gene Annotation ◽  
Tissue Expression ◽  
Mendelian Inheritance ◽  
Disease Genes ◽  
Human Tissues ◽  
Sequencing Data ◽  
Protein Coding ◽  
Neurogenetic Disorders ◽  
Different Tissues

Growing evidence suggests that human gene annotation remains incomplete; however, it is unclear how this affects different tissues and our understanding of different disorders. Here, we detect previously unannotated transcription from Genotype-Tissue Expression RNA sequencing data across 41 human tissues. We connect this unannotated transcription to known genes, confirming that human gene annotation remains incomplete, even among well-studied genes including 63% of the Online Mendelian Inheritance in Man–morbid catalog and 317 neurodegeneration-associated genes. We find the greatest abundance of unannotated transcription in brain and genes highly expressed in brain are more likely to be reannotated. We explore examples of reannotated disease genes, such as SNCA, for which we experimentally validate a previously unidentified, brain-specific, potentially protein-coding exon. We release all tissue-specific transcriptomes through vizER: http://rytenlab.com/browser/app/vizER. We anticipate that this resource will facilitate more accurate genetic analysis, with the greatest impact on our understanding of Mendelian and complex neurogenetic disorders.

scholarly journals Systematic determination of the mitochondrial proportion in human and mice tissues for single-cell RNA-sequencing data quality control

2020 ◽  
Author(s):  
Daniel Osorio ◽  
James J Cai
Keyword(s):  
Quality Control ◽  
Data Analysis ◽  
Single Cell ◽  
Cell Types ◽  
Supplementary Information ◽  
Human Tissues ◽  
Data Quality Control ◽  
Sequencing Data ◽  
Mouse Tissues ◽  
Systematic Determination

Abstract Motivation Quality control (QC) is a critical step in single-cell RNA-seq (scRNA-seq) data analysis. Low-quality cells are removed from the analysis during the QC process to avoid misinterpretation of the data. An important QC metric is the mitochondrial proportion (mtDNA%), which is used as a threshold to filter out low-quality cells. Early publications in the field established a threshold of 5% and since then, it has been used as a default in several software packages for scRNA-seq data analysis, and adopted as a standard in many scRNA-seq studies. However, the validity of using a uniform threshold across different species, single-cell technologies, tissues and cell types has not been adequately assessed. Results We systematically analyzed 5 530 106 cells reported in 1349 annotated datasets available in the PanglaoDB database and found that the average mtDNA% in scRNA-seq data across human tissues is significantly higher than in mouse tissues. This difference is not confounded by the platform used to generate the data. Based on this finding, we propose new reference values of the mtDNA% for 121 tissues of mouse and 44 tissues of humans. In general, for mouse tissues, the 5% threshold performs well to distinguish between healthy and low-quality cells. However, for human tissues, the 5% threshold should be reconsidered as it fails to accurately discriminate between healthy and low-quality cells in 29.5% (13 of 44) tissues analyzed. We conclude that omitting the mtDNA% QC filter or adopting a suboptimal mtDNA% threshold may lead to erroneous biological interpretations of scRNA-seq data. Availabilityand implementation The code used to download datasets, perform the analyzes and produce the figures is available at https://github.com/dosorio/mtProportion. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Systematic determination of the mitochondrial proportion in human and mice tissues for single-cell RNA sequencing data quality control

2020 ◽  
Author(s):  
Daniel Osorio ◽  
James J. Cai
Keyword(s):  
Quality Control ◽  
Data Analysis ◽  
Single Cell ◽  
Cell Types ◽  
Supplementary Information ◽  
Human Tissues ◽  
Data Quality Control ◽  
Sequencing Data ◽  
Mouse Tissues ◽  
Systematic Determination

AbstractMotivationQuality control (QC) is a critical step in single-cell RNA-seq (scRNA-seq) data analysis. Low-quality cells are removed from the analysis during the QC process to avoid misinterpretation of the data. One of the important QC metrics is the mitochondrial proportion (mtDNA%), which is used as a threshold to filter out low-quality cells. Early publications in the field established a threshold of 5% and since then, it has been used as a default in several software packages for scRNA-seq data analysis and adopted as a standard in many scRNA-seq studies. However, the validity of using a uniform threshold across different species, single-cell technologies, tissues, and cell types has not been adequately assessed.ResultsWe systematically analyzed 5,530,106 cells reported in 1,349 annotated datasets available in the PanglaoDB database and found that the average mtDNA% in scRNA-seq data across human tissues is significantly higher than in mouse tissues. This difference is not confounded by the platform used to generate the data. Based on this finding, we propose new reference values of the mtDNA% for 121 tissues of mice and 44 tissues of humans. In general, for mouse tissues, the 5% threshold performs well to distinguish between healthy and low-quality cells. However, for human tissues, the 5% threshold should be reconsidered as it fails to accurately discriminate between healthy and low-quality cells in 29.5% (13 of 44) tissues analyzed. We conclude that omitting the mtDNA% QC filter or adopting a suboptimal mtDNA% threshold may lead to erroneous biological interpretations of scRNA-seq data.AvailabilityThe code used to download datasets, perform the analyzes, and produce the figures is available at https://github.com/dosorio/[email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals Polymorphic mobile element insertions contribute to gene expression and alternative splicing in human tissues

2020 ◽  
Author(s):  
Xiaolong Cao ◽  
Yeting Zhang ◽  
Lindsay M Payer ◽  
Hannah Lords ◽  
Jared P Steranka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Genome Sequencing ◽  
Quantitative Trait ◽  
Mobile Element ◽  
Whole Genome Sequencing Data ◽  
Whole Genome ◽  
Human Tissues ◽  
Sequencing Data ◽  
Different Tissues

AbstractBackgroundMobile elements are a major source of human structural variants and some mobile elements can regulate gene expression and alternative splicing. However, the impact of polymorphic mobile element insertions (pMEIs) on gene expression and splicing in diverse human tissues has not been thoroughly studied. The multi-tissue gene expression and whole genome sequencing data generated by the Genotype-Tissue Expression (GTEx) project provide a great opportunity to systematic determine pMEIs’ role in gene expression regulation in human tissues.ResultsUsing the GTEx whole genome sequencing data, we identified 20,545 high-quality pMEIs from 639 individuals. We then identified pMEI-associated expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) in 48 tissues by joint analysis of variants including pMEIs, single-nucleotide polymorphisms, and insertions/deletions. pMEIs were predicted to be the potential causal variant for 3,522 of the 30,147 significant eQTLs, and 3,717 of the 21,529 significant sQTLs. The pMEIs associated eQTLs and sQTLs show high level of tissue-specificity, and the pMEIs were enriched in the proximity of affected genes and in regulatory elements. Using reporter assays, we confirmed that several pMEIs associated with eQTLs and sQTLs can alter gene expression levels and isoform proportions.ConclusionOverall, our study shows that pMEIs are associated with thousands of gene expression and splicing variations in different tissues, and pMEIs could have a significant role in regulating tissue-specific gene expression/splicing. Detailed mechanisms for pMEI’s role in gene regulation in different tissues will be an important direction for future human genomic studies.

Microstructural comparison of synthetic bioceramics with natural bioceramics

1991 ◽  
Vol 49 ◽  
pp. 38-39
Author(s):  
Shulin Wen ◽  
Jingwei Feng ◽  
A. Krajewski ◽  
A. Ravaglioli
Keyword(s):  
Recent Work ◽  
Human Body ◽  
Human Tissues ◽  
Main Constituent ◽  
Laboratory Furnace ◽  
Chinese Adult ◽  
Human Enamel ◽  
Biological Compatibility ◽  
Synthetic Hydroxyapatite ◽  
Synthetic Work

Hydroxyapatite bioceramics has attracted many material scientists as it is the main constituent of the bone and the teeth in human body. The synthesis of the bioceramics has been performed for years. Nowadays, the synthetic work is not only focused on the hydroapatite but also on the fluorapatite and chlorapatite bioceramics since later materials have also biological compatibility with human tissues; and they may also be very promising for clinic purpose. However, in comparison of the synthetic bioceramics with natural one on microstructure, a great differences were observed according to our previous results. We have investigated these differences further in this work since they are very important to appraise the synthetic bioceramics for their clinic application.The synthetic hydroxyapatite and chlorapatite were prepared according to A. Krajewski and A. Ravaglioli and their recent work. The briquettes from different hydroxyapatite or chlorapatite powders were fired in a laboratory furnace at the temperature of 900-1300°C. The samples of human enamel selected for the comparison with synthetic bioceramics were from Chinese adult teeth.

Study on erythrocytes by SEM photogrammetry (SEMP) technique

1990 ◽  
Vol 48 (3) ◽  
pp. 724-725
Author(s):  
Tong Wensheng ◽  
Lu Lianhuang ◽  
Zhang Zhijun
Keyword(s):  
Quantitative Analysis ◽  
Cell Membrane ◽  
Clinical Diagnosis ◽  
Human Body ◽  
Blood Cells ◽  
Three Dimensional ◽  
Normal Person ◽  
Blood Disease ◽  
Computation Technique ◽  
Important Basis

This is a combined study of two diffirent branches, photogrammetry and morphology of blood cells. The three dimensional quantitative analysis of erythrocytes using SEMP technique, electron computation technique and photogrammetry theory has made it possible to push the study of mophology of blood cells from LM, TEM, SEM to a higher stage, that of SEM P. A new path has been broken for deeply study of morphology of blood cells.In medical view, the abnormality of the quality and quantity of erythrocytes is one of the important changes of blood disease. It shows the abnormal blood—making function of the human body. Therefore, the study of the change of shape on erythrocytes is the indispensable and important basis of reference in the clinical diagnosis and research of blood disease.The erythrocytes of one normal person, three PNH Patients and one AA patient were used in this experiment. This research determines the following items: Height;Length of two axes (long and short), ratio; Crevice in depth and width of cell membrane; Circumference of erythrocytes; Isoline map of erythrocytes; Section map of erythrocytes.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

scholarly journals In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kolja Becker ◽  
Holger Klein ◽  
Eric Simon ◽  
Coralie Viollet ◽  
Christian Haslinger ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Expression Profiles ◽  
Cell Types ◽  
Sequencing Data ◽  
Disease Stages ◽  
Post Transcriptional Regulation

AbstractDiabetic Retinopathy (DR) is among the major global causes for vision loss. With the rise in diabetes prevalence, an increase in DR incidence is expected. Current understanding of both the molecular etiology and pathways involved in the initiation and progression of DR is limited. Via RNA-Sequencing, we analyzed mRNA and miRNA expression profiles of 80 human post-mortem retinal samples from 43 patients diagnosed with various stages of DR. We found differentially expressed transcripts to be predominantly associated with late stage DR and pathways such as hippo and gap junction signaling. A multivariate regression model identified transcripts with progressive changes throughout disease stages, which in turn displayed significant overlap with sphingolipid and cGMP–PKG signaling. Combined analysis of miRNA and mRNA expression further uncovered disease-relevant miRNA/mRNA associations as potential mechanisms of post-transcriptional regulation. Finally, integrating human retinal single cell RNA-Sequencing data revealed a continuous loss of retinal ganglion cells, and Müller cell mediated changes in histidine and β-alanine signaling. While previously considered primarily a vascular disease, attention in DR has shifted to additional mechanisms and cell-types. Our findings offer an unprecedented and unbiased insight into molecular pathways and cell-specific changes in the development of DR, and provide potential avenues for future therapeutic intervention.

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