scholarly journals Determinants of transcription factor regulatory range

2019 ◽  
Author(s):  
Chen-Hao Chen ◽  
Rongbin Zheng ◽  
Jingyu Fan ◽  
Myles Brown ◽  
Jun S. Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Long Range ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Chromatin State ◽  
Specific Cell ◽  
Regulatory Influence ◽  
State Dependent ◽  
Functional Classes

AbstractTo characterize the genomic distances over which transcription factors (TFs) influence gene expression, we examined thousands of TF and histone modification ChIP-seq datasets and thousands of gene expression profiles. A model integrating these data revealed two classes of TF: one with short-range regulatory influence, the other with long-range regulatory influence. The two TF classes also had distinct chromatin-binding preferences and auto-regulatory properties. The regulatory range of a single TF bound within different topologically associating domains (TADs) depended on intrinsic TAD properties such as local gene density and G/C content, but also on the TAD chromatin state in specific cell types. Our results provide evidence that most TFs belong to one of these two functional classes, and that the regulatory range of long-range TFs is chromatin-state dependent. Thus, consideration of TF type, distance-to-target, and chromatin context is likely important in identifying TF regulatory targets and interpreting GWAS and eQTL SNPs.

scholarly journals Self-reporting transposons enable simultaneous readout of gene expression and transcription factor binding in single cells

2019 ◽  
Author(s):  
Arnav Moudgil ◽  
Michael N. Wilkinson ◽  
Xuhua Chen ◽  
June He ◽  
Alex J. Cammack ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Single Cell ◽  
Binding Sites ◽  
Expression Profiles ◽  
Single Cells ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Specific Cell

AbstractIn situ measurements of transcription factor (TF) binding are confounded by cellular heterogeneity and represent averaged profiles in complex tissues. Single cell RNA-seq (scRNA-seq) is capable of resolving different cell types based on gene expression profiles, but no technology exists to directly link specific cell types to the binding pattern of TFs in those cell types. Here, we present self-reporting transposons (SRTs) and their use in single cell calling cards (scCC), a novel assay for simultaneously capturing gene expression profiles and mapping TF binding sites in single cells. First, we show how the genomic locations of SRTs can be recovered from mRNA. Next, we demonstrate that SRTs deposited by the piggyBac transposase can be used to map the genome-wide localization of the TFs SP1, through a direct fusion of the two proteins, and BRD4, through its native affinity for piggyBac. We then present the scCC method, which maps SRTs from scRNA-seq libraries, thus enabling concomitant identification of cell types and TF binding sites in those same cells. As a proof-of-concept, we show recovery of cell type-specific BRD4 and SP1 binding sites from cultured cells. Finally, we map Brd4 binding sites in the mouse cortex at single cell resolution, thus establishing a new technique for studying TF biology in situ.

scholarly journals Analysis of the transcriptome of bovine endometrial cells isolated by laser micro-dissection (1): specific signatures of stromal, glandular and luminal epithelial cells

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Wiruntita Chankeaw ◽  
Sandra Lignier ◽  
Christophe Richard ◽  
Theodoros Ntallaris ◽  
Mariam Raliou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Localization ◽  
Expression Profiles ◽  
Cell Types ◽  
Molecular Signature ◽  
Receptor Protein ◽  
Specific Gene ◽  
Specific Cell ◽  
Biological Processes ◽  
Endometrial Cells

Abstract Background A number of studies have examined mRNA expression profiles of bovine endometrium at estrus and around the peri-implantation period of pregnancy. However, to date, these studies have been performed on the whole endometrium which is a complex tissue. Consequently, the knowledge of cell-specific gene expression, when analysis performed with whole endometrium, is still weak and obviously limits the relevance of the results of gene expression studies. Thus, the aim of this study was to characterize specific transcriptome of the three main cell-types of the bovine endometrium at day-15 of the estrus cycle. Results In the RNA-Seq analysis, the number of expressed genes detected over 10 transcripts per million was 6622, 7814 and 8242 for LE, GE and ST respectively. ST expressed exclusively 1236 genes while only 551 transcripts were specific to the GE and 330 specific to LE. For ST, over-represented biological processes included many regulation processes and response to stimulus, cell communication and cell adhesion, extracellular matrix organization as well as developmental process. For GE, cilium organization, cilium movement, protein localization to cilium and microtubule-based process were the only four main biological processes enriched. For LE, over-represented biological processes were enzyme linked receptor protein signaling pathway, cell-substrate adhesion and circulatory system process. Conclusion The data show that each endometrial cell-type has a distinct molecular signature and provide a significantly improved overview on the biological process supported by specific cell-types. The most interesting result is that stromal cells express more genes than the two epithelial types and are associated with a greater number of pathways and ontology terms.

scholarly journals Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bing He ◽  
Ping Chen ◽  
Sonia Zambrano ◽  
Dina Dabaghie ◽  
Yizhou Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Human Kidney ◽  
Cell Types ◽  
Model Organisms ◽  
Mural Cell ◽  
Glomerular Cell ◽  
Individual Gene ◽  
The Individual

AbstractMolecular characterization of the individual cell types in human kidney as well as model organisms are critical in defining organ function and understanding translational aspects of biomedical research. Previous studies have uncovered gene expression profiles of several kidney glomerular cell types, however, important cells, including mesangial (MCs) and glomerular parietal epithelial cells (PECs), are missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we use Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis reveals genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells. Importantly, we detect heterogeneity in glomerulus-associated Pdgfrb-expressing cells, including bona fide intraglomerular MCs with the functionally active phagocytic molecular machinery, as well as a unique mural cell type located in the central stalk region of the glomerulus tuft. Furthermore, we observe remarkable species differences in the individual gene expression profiles of defined glomerular cell types that highlight translational challenges in the field and provide a guide to design translational studies.

Gene Expression Regulation underlying Osteo-, Adipo-, and Chondro-Genic Lineage Commitment of Human Mesenchymal Stem Cells

2013 ◽  
pp. 76-94 ◽  
Author(s):  
Ana M. Sotoca ◽  
Michael Weber ◽  
Everardus J. J. van Zoelen
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Expression Regulation ◽  
Expression Profiles ◽  
Human Mesenchymal Stem Cells ◽  
Gene Expression Profiles ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Lineage Commitment

Human mesenchymal stem cells have a high potential in regenerative medicine. They can be isolated from a variety of adult tissues, including bone marrow, and can be differentiated into multiple cell types of the mesodermal lineage, including adipocytes, osteocytes, and chondrocytes. Stem cell differentiation is controlled by a process of interacting lineage-specific and multipotent genes. In this chapter, the authors use full genome microarrays to explore gene expression profiles in the process of Osteo-, Adipo-, and Chondro-Genic lineage commitment of human mesenchymal stem cells.

scholarly journals Aortic heterogeneity across segments and under high fat/salt/glucose conditions at the single-cell level

2020 ◽  
Vol 7 (5) ◽  
pp. 881-896 ◽  
Author(s):  
Dongxu He ◽  
Aiqin Mao ◽  
Chang-Bo Zheng ◽  
Hao Kan ◽  
Ka Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
The Body ◽  
Dietary Salt ◽  
High Fat ◽  
High Blood Glucose ◽  
Thoracic And Abdominal

Abstract The aorta, with ascending, arch, thoracic and abdominal segments, responds to the heartbeat, senses metabolites and distributes blood to all parts of the body. However, the heterogeneity across aortic segments and how metabolic pathologies change it are not known. Here, a total of 216 612 individual cells from the ascending aorta, aortic arch, and thoracic and abdominal segments of mouse aortas under normal conditions or with high blood glucose levels, high dietary salt, or high fat intake were profiled using single-cell RNA sequencing. We generated a compendium of 10 distinct cell types, mainly endothelial (EC), smooth muscle (SMC), stromal and immune cells. The distributions of the different cells and their intercommunication were influenced by the hemodynamic microenvironment across anatomical segments, and the spatial heterogeneity of ECs and SMCs may contribute to differential vascular dilation and constriction that were measured by wire myography. Importantly, the composition of aortic cells, their gene expression profiles and their regulatory intercellular networks broadly changed in response to high fat/salt/glucose conditions. Notably, the abdominal aorta showed the most dramatic changes in cellular composition, particularly involving ECs, fibroblasts and myeloid cells with cardiovascular risk factor-related regulons and gene expression networks. Our study elucidates the nature and range of aortic cell diversity, with implications for the treatment of metabolic pathologies.

scholarly journals Gene Expression in Porphyromonas gingivalis after Contact with Human Epithelial Cells

2005 ◽  
Vol 73 (4) ◽  
pp. 2327-2335 ◽  
Author(s):  
Yumiko Hosogi ◽  
Margaret J. Duncan
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Porphyromonas Gingivalis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Adverse Conditions ◽  
Human Epithelial Cells ◽  
Host Epithelium ◽  
Shock Proteins

ABSTRACT Porphyromonas gingivalis, a gram-negative oral anaerobe, is strongly associated with adult periodontitis. The adherence of the organism to host epithelium signals changes in both cell types as bacteria initiate infection and colonization and epithelial cells rally their defenses. We hypothesized that the expression of a defined set of P. gingivalis genes would be consistently up-regulated during infection of HEp-2 human epithelial cells. P. gingivalis genome microarrays were used to compare the gene expression profiles of bacteria that adhered to HEp-2 cells and bacteria that were incubated alone. Genes whose expression was temporally up-regulated included those involved in the oxidative stress response and those encoding heat shock proteins that are essential to maintaining cell viability under adverse conditions. The results suggest that contact with epithelial cells induces in P. gingivalis stress-responsive pathways that promote the survival of the bacterium.

scholarly journals Porcine colonoids and enteroids keep the memory of their origin during regeneration.

2021 ◽  
Author(s):  
Alicia M. Barnett ◽  
Jane A. Mullaney ◽  
Charlotte Hendriks ◽  
Lisa Le Borgne ◽  
Warren C. McNabb ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Transporter ◽  
Expression Profiles ◽  
Cell Types ◽  
Specific Cell ◽  
Stem Cell Markers ◽  
Culture Methods ◽  
Glucose Transporter 1 ◽  
Expression Levels

The development of alternative in vitro culture methods has increased in the last decade as three-dimensional organoids of various tissues, including those of the small and large intestines. Due to their multicellular composition, organoids offer advantages over traditionally used immortalized or primary cell lines. However, organoids must be accurate models of their tissues of origin. This study compared gene expression profiles with respect to markers of specific cell-types (stem-cells, enterocytes, goblet and enteroendocrine cells) and barrier maturation (tight junctions) of colonoid and enteroid cultures with their tissues of origin, and colonoids with enteroids. Colonoids derived from three healthy pigs formed multi-lobed structures with a monolayer of cells similar to the crypt structures in colonic tissue. Colonoid and enteroid gene expression signatures were more similar to those found for the tissues of their origin than to each other. However, relative to their derived tissues, organoids had increased gene expression levels of stem-cell markers Sox9 and Lgr5 encoding Sex determining region Y-box 9 and leucine-rich repeat-containing G-protein coupled rector 5, respectively. In contrast, expression levels of Occl and Zo1 encoding occludin and zonula occludens 1 respectively, were decreased. Expression levels of the cell lineage markers Atoh1, Cga and Muc2 encoding atonal homolog 1, chromogranin A and mucin 2 respectively, were decreased in colonoids, while Sglt1 and Apn encoding sodium-glucose transporter 1 and aminopeptidase A respectively, were decreased in enteroids. These results indicate colonoid and enteroid cultures were predominantly comprised of undifferentiated cell-types with decreased barrier maturation relative to their tissues of origin.

scholarly journals Bayesian log-normal deconvolution for enhanced in silico microdissection of bulk gene expression data

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bárbara Andrade Barbosa ◽  
Saskia D. van Asten ◽  
Ji Won Oh ◽  
Arantza Farina-Sarasqueta ◽  
Joanne Verheij ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Expression Data ◽  
Cell Type ◽  
Expression Variability ◽  
Variable Nature ◽  
Log Normal

AbstractDeconvolution of bulk gene expression profiles into the cellular components is pivotal to portraying tissue’s complex cellular make-up, such as the tumor microenvironment. However, the inherently variable nature of gene expression requires a comprehensive statistical model and reliable prior knowledge of individual cell types that can be obtained from single-cell RNA sequencing. We introduce BLADE (Bayesian Log-normAl Deconvolution), a unified Bayesian framework to estimate both cellular composition and gene expression profiles for each cell type. Unlike previous comprehensive statistical approaches, BLADE can handle > 20 types of cells due to the efficient variational inference. Throughout an intensive evaluation with > 700 simulated and real datasets, BLADE demonstrated enhanced robustness against gene expression variability and better completeness than conventional methods, in particular, to reconstruct gene expression profiles of each cell type. In summary, BLADE is a powerful tool to unravel heterogeneous cellular activity in complex biological systems from standard bulk gene expression data.

scholarly journals Distinct properties in ventral pallidum projection neuron subtypes

2021 ◽  
Author(s):  
Nimrod Bernat ◽  
Rianne Campbell ◽  
Hyungwoo Nam ◽  
Mahashweta Basu ◽  
Tal Odesser ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Critical Role ◽  
Gene Expression Profiles ◽  
Cell Types ◽  
Projection Neuron ◽  
Brain Regions ◽  
Ventral Pallidum ◽  
Lateral Habenula

The ventral pallidum (VP), a major component of the basal ganglia, plays a critical role in motivational disorders. It sends projections to many different brain regions but it is not yet known whether and how these projections differ in their cellular properties, gene expression patterns, connectivity and role in reward seeking. In this study, we focus on four major outputs of the VP - to the lateral hypothalamus (LH), ventral tegmental area (VTA), mediodorsal thalamus (MDT), and lateral habenula (LHb) - and examine the differences between them in 1) baseline gene expression profiles using projection-specific RNA-sequencing; 2) physiological parameters using whole-cell patch clamp; and 3) their influence on cocaine reward using chemogenetic tools. We show that these four VP efferents differ in all three aspects and highlight specifically differences between the projections to the LH and the VTA. These two projections originate largely from separate populations of neurons, express distinct sets of genes related to neurobiological functions, and show opposite physiological and behavioral properties. Collectively, our data demonstrates for the first time that VP neurons exhibit distinct molecular and cellular profiles in a projection-specific manner, suggesting that they represent different cell types.

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