scholarly journals A draft network of ligand–receptor-mediated multicellular signalling in human

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Jordan A. Ramilowski ◽  
Tatyana Goldberg ◽  
Jayson Harshbarger ◽  
Edda Kloppmann ◽  
Marina Lizio ◽  
...  
Keyword(s):  
Large Scale ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Surface Receptors ◽  
Signalling Network ◽  
Multiple Cell ◽  
Autocrine Signalling ◽  
Multiple Ligand

Abstract Cell-to-cell communication across multiple cell types and tissues strictly governs proper functioning of metazoans and extensively relies on interactions between secreted ligands and cell-surface receptors. Herein, we present the first large-scale map of cell-to-cell communication between 144 human primary cell types. We reveal that most cells express tens to hundreds of ligands and receptors to create a highly connected signalling network through multiple ligand–receptor paths. We also observe extensive autocrine signalling with approximately two-thirds of partners possibly interacting on the same cell type. We find that plasma membrane and secreted proteins have the highest cell-type specificity, they are evolutionarily younger than intracellular proteins, and that most receptors had evolved before their ligands. We provide an online tool to interactively query and visualize our networks and demonstrate how this tool can reveal novel cell-to-cell interactions with the prediction that mast cells signal to monoblastic lineages via the CSF1–CSF1R interacting pair.

scholarly journals Predicting cell-to-cell communication networks using NATMI

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Rui Hou ◽  
Elena Denisenko ◽  
Huan Ting Ong ◽  
Jordan A. Ramilowski ◽  
Alistair R. R. Forrest
Keyword(s):  
Single Cell ◽  
Communication Networks ◽  
Cell Communication ◽  
Cost Effective ◽  
Cell Types ◽  
Sequencing Technologies ◽  
Multiple Cell ◽  
Multicellular Interactions ◽  
Autocrine Signalling ◽  
Different Cell Types

Abstract Development of high throughput single-cell sequencing technologies has made it cost-effective to profile thousands of cells from diverse samples containing multiple cell types. To study how these different cell types work together, here we develop NATMI (Network Analysis Toolkit for Multicellular Interactions). NATMI uses connectomeDB2020 (a database of 2293 manually curated ligand-receptor pairs with literature support) to predict and visualise cell-to-cell communication networks from single-cell (or bulk) expression data. Using multiple published single-cell datasets we demonstrate how NATMI can be used to identify (i) the cell-type pairs that are communicating the most (or most specifically) within a network, (ii) the most active (or specific) ligand-receptor pairs active within a network, (iii) putative highly-communicating cellular communities and (iv) differences in intercellular communication when profiling given cell types under different conditions. Furthermore, analysis of the Tabula Muris (organism-wide) atlas confirms our previous prediction that autocrine signalling is a major feature of cell-to-cell communication networks, while also revealing that hundreds of ligands and their cognate receptors are co-expressed in individual cells suggesting a substantial potential for self-signalling.

scholarly journals Escape from X-inactivation in twins exhibits intra- and inter-individual variability across tissues and is heritable

2021 ◽  
Author(s):  
Antonino Zito ◽  
Amy L Roberts ◽  
Alessia Visconti ◽  
Niccolo' Rossi ◽  
Rosa Andres-Ejarque ◽  
...  
Keyword(s):  
X Chromosome ◽  
Large Scale ◽  
Genetic Factors ◽  
Immune Cell ◽  
Cell Types ◽  
Individual Variability ◽  
Healthy Population ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Escape From X Inactivation

X-chromosome inactivation (XCI) silences one X-chromosome in female cells to balance sex-differences in X-dosage. A subset of X-linked genes escape XCI, but the extent to which this phenomenon occurs and how it varies across tissues and in a population is as yet unclear. In order to characterize the incidence and variability of escape across individuals and tissues, we conducted a large scale transcriptomic study of XCI escape in adipose, skin, lymphoblastoid cell lines (LCLs) and immune cells in 248 twins drawn from a healthy population cohort. We identify 159 X-linked genes with detectable escape, of which 54 genes, including 19 lncRNAs, were not previously known to escape XCI. Across tissues we find a range of tissue-specificity, with 11% of genes escaping XCI constitutively across tissues and 24% demonstrating tissue-restricted escape, including genes with cell-type specific escape between immune cell types (B, T-CD4+, T-CD8+ and NK cells) of the same individual. Escape genes interact with autosomal-encoded proteins and are involved in varied biological processes such as gene regulation. We find substantial variability in escape between individuals. 49% of genes show inter-individual variability in escape, indicating escape from XCI is an under-appreciated source of gene expression differences. We utilized twin models to investigate the role of genetics in variable escape. Overall, monozygotic (MZ) twin pairs share more similar escape than dizygotic twin pairs, indicating that genetic factors underlie differences in escape across individuals. However, we also identify instances of discordant XCI within MZ co-twin pairs, suggesting that environmental factors also influence escape. Thus, XCI escape may be shaped by an interplay of genetic factors with tissue- and cell type-specificity, and environment. These results illuminate an intricate phenotype whose characterization aids understanding the basis of variable trait expressivity in females.

scholarly journals QTLbase: an integrative resource for quantitative trait loci across multiple human molecular phenotypes

2019 ◽  
Vol 48 (D1) ◽  
pp. D983-D991 ◽  
Author(s):  
Zhanye Zheng ◽  
Dandan Huang ◽  
Jianhua Wang ◽  
Ke Zhao ◽  
Yao Zhou ◽  
...  
Keyword(s):  
Quantitative Trait ◽  
Large Scale ◽  
Cell Types ◽  
Tissue Cell ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Significant Qtls ◽  
Functional Variants ◽  
Trait Locus ◽  
Molecular Phenotypes

Abstract Recent advances in genome sequencing and functional genomic profiling have promoted many large-scale quantitative trait locus (QTL) studies, which connect genotypes with tissue/cell type-specific cellular functions from transcriptional to post-translational level. However, no comprehensive resource can perform QTL lookup across multiple molecular phenotypes and investigate the potential cascade effect of functional variants. We developed a versatile resource, named QTLbase, for interpreting the possible molecular functions of genetic variants, as well as their tissue/cell-type specificity. Overall, QTLbase has five key functions: (i) curating and compiling genome-wide QTL summary statistics for 13 human molecular traits from 233 independent studies; (ii) mapping QTL-relevant tissue/cell types to 78 unified terms according to a standard anatomogram; (iii) normalizing variant and trait information uniformly, yielding >170 million significant QTLs; (iv) providing a rich web client that enables phenome- and tissue-wise visualization; and (v) integrating the most comprehensive genomic features and functional predictions to annotate the potential QTL mechanisms. QTLbase provides a one-stop shop for QTL retrieval and comparison across multiple tissues and multiple layers of molecular complexity, and will greatly help researchers interrogate the biological mechanism of causal variants and guide the direction of functional validation. QTLbase is freely available at http://mulinlab.org/qtlbase.

Specificity of gene expression in adipocytes

1985 ◽  
Vol 5 (2) ◽  
pp. 419-421
Author(s):  
K M Zezulak ◽  
H Green
Keyword(s):  
Gene Expression ◽  
Cell Types ◽  
Cell Type ◽  
3T3 Cells ◽  
Cell Type Specificity ◽  
Number Of Genes ◽  
Enhanced Expression ◽  
Adipose Cells ◽  
Distinctive Phenotype

During the differentiation of preadipose 3T3 cells into adipose cells, the mRNAs for three proteins increase strikingly in abundance. To determine the degree of cell-type specificity in the expression of these mRNAs, we estimated their abundances in several nonadipose tissues of the mouse. None of these mRNAs was strictly confined to adipocytes, but the ensemble of three mRNAs was rather specific to adipocytes. Insofar as is revealed by these three markers, the distinctive phenotype of adipocytes is the result of the enhanced expression of a number of genes, none of which is completely silent in all other cell types.

scholarly journals A scalable platform for the development of cell-type-specific viral drivers

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Sinisa Hrvatin ◽  
Christopher P Tzeng ◽  
M Aurel Nagy ◽  
Hume Stroud ◽  
Charalampia Koutsioumpa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heterologous Gene Expression ◽  
High Specificity ◽  
Cell Types ◽  
Regulatory Elements ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Cell Type Specific ◽  
The Many ◽  
Dna Regulatory Elements

Enhancers are the primary DNA regulatory elements that confer cell type specificity of gene expression. Recent studies characterizing individual enhancers have revealed their potential to direct heterologous gene expression in a highly cell-type-specific manner. However, it has not yet been possible to systematically identify and test the function of enhancers for each of the many cell types in an organism. We have developed PESCA, a scalable and generalizable method that leverages ATAC- and single-cell RNA-sequencing protocols, to characterize cell-type-specific enhancers that should enable genetic access and perturbation of gene function across mammalian cell types. Focusing on the highly heterogeneous mammalian cerebral cortex, we apply PESCA to find enhancers and generate viral reagents capable of accessing and manipulating a subset of somatostatin-expressing cortical interneurons with high specificity. This study demonstrates the utility of this platform for developing new cell-type-specific viral reagents, with significant implications for both basic and translational research.

scholarly journals A nervous system-specific subnuclear organelle in Caenorhabditis elegans

Genetics ◽  
2021 ◽  
Vol 217 (1) ◽  
Author(s):  
Kenneth Pham ◽  
Neda Masoudi ◽  
Eduardo Leyva-Díaz ◽  
Oliver Hobert
Keyword(s):  
Nervous System ◽  
Caenorhabditis Elegans ◽  
Homeobox Gene ◽  
Cell Types ◽  
Nuclear Bodies ◽  
Loss Of Function ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Splicing Speckles ◽  
Polycomb Bodies

Abstract We describe here phase-separated subnuclear organelles in the nematode Caenorhabditis elegans, which we term NUN (NUclear Nervous system-specific) bodies. Unlike other previously described subnuclear organelles, NUN bodies are highly cell type specific. In fully mature animals, 4–10 NUN bodies are observed exclusively in the nucleus of neuronal, glial and neuron-like cells, but not in other somatic cell types. Based on co-localization and genetic loss of function studies, NUN bodies are not related to other previously described subnuclear organelles, such as nucleoli, splicing speckles, paraspeckles, Polycomb bodies, promyelocytic leukemia bodies, gems, stress-induced nuclear bodies, or clastosomes. NUN bodies form immediately after cell cycle exit, before other signs of overt neuronal differentiation and are unaffected by the genetic elimination of transcription factors that control many other aspects of neuronal identity. In one unusual neuron class, the canal-associated neurons, NUN bodies remodel during larval development, and this remodeling depends on the Prd-type homeobox gene ceh-10. In conclusion, we have characterized here a novel subnuclear organelle whose cell type specificity poses the intriguing question of what biochemical process in the nucleus makes all nervous system-associated cells different from cells outside the nervous system.

Prenet: Predictive network from ATAC-SEQ data

2020 ◽  
Vol 18 (01) ◽  
pp. 2040003 ◽  
Author(s):  
Nazmus Salehin ◽  
Patrick P. L. Tam ◽  
Pierre Osteil
Keyword(s):  
Regulatory Network ◽  
State Of The Art ◽  
Cell Types ◽  
Cell Type ◽  
Regulatory Pathways ◽  
Novel Approach ◽  
Multiple Cell ◽  
Bona Fide ◽  
Gene Regulatory ◽  
Accessible Chromatin

Assays for transposase-accessible chromatin sequencing (ATAC-seq) provides an innovative approach to study chromatin status in multiple cell types. Moreover, it is also possible to efficiently extract differentially accessible chromatin (DACs) regions by using state-of-the-art algorithms (e.g. DESeq2) to predict gene activity in specific samples. Furthermore, it has recently been shown that small dips in sequencing peaks can be attributed to the binding of transcription factors. These dips, also known as footprints, can be used to identify trans-regulating interactions leading to gene expression. Current protocols used to identify footprints (e.g. pyDNAse and HINT-ATAC) have shown limitations resulting in the discovery of many false positive footprints. We generated a novel approach to identify genuine footprints within any given ATAC-seq dataset. Herein, we developed a new pipeline embedding DACs together with bona fide footprints resulting in the generation of a Predictive gene regulatory Network (PreNet) simply from ATAC-seq data. We further demonstrated that PreNet can be used to unveil meaningful molecular regulatory pathways in a given cell type.

113. DEVELOPMENT OF A METHOD OF SEMINIFEROUS TUBULE TRANSFECTION IN VITRO TO DEFINE POSTMEIOTIC GENE REGULATION

2009 ◽  
Vol 21 (9) ◽  
pp. 32
Author(s):  
S. Danner ◽  
C. Kirchhoff ◽  
R. Ivell
Keyword(s):  
Fluorescent Protein ◽  
Transgenic Animals ◽  
Cell Types ◽  
Seminiferous Tubules ◽  
Gene Promoters ◽  
Cell Type ◽  
Cell Type Specificity ◽  
High Throughput Analysis ◽  
Apparent Lack

Postmeiotically expressed genes in the testis are essential for the proper progression of spermatogenesis, and yet, aside from the construction of individual transgenic mice using specific promoters to drive reporter plasmids, there are only very limited possibilities for relevant and quantitative analysis of gene promoters. This is due to the special nature of post-meiotic haploid cells, which to date are not represented in any appropriate cell-lines. Here we report the development of novel methodology using isolated and cultured rat seminiferous tubules in a multiwell format, into which promoter-reporter constructs can be introduced by a combination of microinjection and electroporation. Culture conditions were developed which allowed the continued incubation of isolated rat seminiferous tubules for up to 48h without obvious cell death and loss of post-meiotic cells. Transfection of intact seminiferous tubules by microinjection and electroporation was optimized to achieve high expression efficiencies of control plasmids, using either fluorescent protein or luciferase as reporters, thereby allowing both morphological as well as quantitative assessment. Successful transfection was achieved into all cell types except for mature spermatozoa. However, there appeared to be only limited cell-type specificity for the promoters used, even though these had appeared to be specific when used in transgenic animals. We have devised a methodology which allows relatively high throughput analysis of post-meiotic gene promoters into primary cells of intact seminiferous tubules. An apparent lack of cell-type specificity suggests that the gene fragments used do not contain sufficient targeting information, or that the transient episomal expression of the constructs does not encourage appropriate expression specificity. The results also highlight the doubtful interpretation of many studies using heterologous transfection systems to analyse post-meiotically expressed genes.

scholarly journals Complex Cell Type-Specific Roles of Autophagy in Liver Fibrosis and Cirrhosis

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 225
Author(s):  
Tzu-Min Hung ◽  
Chih-Chiang Hsiao ◽  
Chih-Wen Lin ◽  
Po-Huang Lee
Keyword(s):  
Liver Fibrosis ◽  
Cell Types ◽  
Degradation Pathway ◽  
Cellular Tissue ◽  
Future Research ◽  
Specific Cell ◽  
Cell Type ◽  
Stage Disease ◽  
Multiple Cell ◽  
End Stage

The lysosomal degradation pathway, or autophagy, plays a fundamental role in cellular, tissue, and organismal homeostasis. A correlation between dysregulated autophagy and liver fibrosis (including end-stage disease, cirrhosis) is well-established. However, both the up and downregulation of autophagy have been implicated in fibrogenesis. For example, the inhibition of autophagy in hepatocytes and macrophages can enhance liver fibrosis, whereas autophagic activity in hepatic stellate cells and reactive ductular cells is permissive towards fibrogenesis. In this review, the contributions of specific cell types to liver fibrosis as well as the mechanisms underlying the effects of autophagy are summarized. In view of the functional effects of multiple cell types on the complex process of hepatic fibrogenesis, integrated approaches that consider the role of autophagy in each liver cell type should be a focus of future research.

scholarly journals An in vivo, neuron-specific approach for pairing translational and epigenetic signatures of early-life exercise

2021 ◽  
Author(s):  
Anthony Mark Raus ◽  
Tyson D Fuller ◽  
Nellie E Nelson ◽  
David A Valientes ◽  
Anita Bayat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Early Life ◽  
Affinity Purification ◽  
Cell Types ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Cell Type Specific ◽  
Induced Changes ◽  
Epigenetic Signatures

Aerobic exercise promotes physiological and molecular adaptations in neurons to influence brain function and behavior. The most well studied neurobiological consequences of exercise are those which underlie exercise-induced improvements in hippocampal memory, including the expression and regulation of the neurotrophic factor Bdnf. Whether aerobic exercise taking place during early-life periods of postnatal brain maturation has similar impacts on gene expression and its regulation remains to be investigated. Using unbiased next-generation sequencing we characterize gene expression programs and their regulation by specific, memory-associated histone modifications during juvenile-adolescent voluntary exercise (ELE). Traditional transcriptomic and epigenomic sequencing approaches have either used heterogeneous cell populations from whole tissue homogenates or flow cytometry for single cell isolation to distinguish cell types / subtypes. These methods fall short in providing cell-type specificity without compromising sequencing depth or procedure-induced changes to cellular phenotype. In this study, we use simultaneous isolation of translating mRNA and nuclear chromatin from a neuron-enriched cell population to more accurately pair ELE-induced changes in gene expression with epigenetic modifications. We employ a line of transgenic mice expressing the NuTRAP (Nuclear Tagging and Translating Ribosome Affinity Purification) cassette under the Emx1 promoter allowing for brain cell-type specificity. We then developed a technique that combines nuclear isolation using Isolation of Nuclei TAgged in Specific Cell Types (INTACT) with Translating Ribosomal Affinity Purification (TRAP) methods to determine cell type-specific epigenetic modifications influencing gene expression programs from a population of Emx1 expressing hippocampal neurons. Data from RNA-seq and CUT&RUN-seq were coupled to evaluate histone modifications influencing the expression of translating mRNA in neurons after early-life exercise (ELE). We also performed separate INTACT and TRAP isolations for validation of our protocol and demonstrate similar molecular functions and biological processes implicated by gene ontology (GO) analysis. Finally, as prior studies use tissue from opposite brain hemispheres to pair transcriptomic and epigenomic data from the same rodent, we take a bioinformatics approach to compare hemispheric differences in gene expression programs and histone modifications altered by by ELE. Our data reveal transcriptional and epigenetic signatures of ELE exposure and identify novel candidate gene-histone modification interactions for further investigation. Importantly, our novel approach of combined INTACT/TRAP methods from the same cell suspension allows for simultaneous transcriptomic and epigenomic sequencing in a cell-type specific manner.

Sign in / Sign up

Export Citation Format

Share Document