scholarly journals Chromatin accessibility differences between alpha, beta, and delta cells identifies common and cell type-specific enhancers

2021 ◽  
Author(s):  
Alex M. Mawla ◽  
Talitha van der Meulen ◽  
Mark O. Huising
Keyword(s):  
Beta Cells ◽  
Islet Cell ◽  
High Throughput Sequencing ◽  
Expression Patterns ◽  
Critical Role ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Alpha Beta ◽  
Cellular Identity ◽  
Delta Cells

AbstractHigh throughput sequencing has enabled the interrogation of the transcriptomic landscape of glucagon-secreting alpha cells, insulin-secreting beta cells, and somatostatin-secreting delta cells. These approaches have furthered our understanding of expression patterns that define healthy or diseased islet cell types and helped explicate some of the intricacies between major islet cell crosstalk and glucose regulation. All three endocrine cell types derive from a common pancreatic progenitor, yet alpha and beta cells have partially opposing functions, and delta cells modulate and control insulin and glucagon release. While gene signatures that define and maintain cellular identity have been widely explored, the underlying epigenetic components are incompletely characterized and understood. Chromatin accessibility and remodeling is a dynamic attribute that plays a critical role to determine and maintain cellular identity. Here, we compare and contrast the chromatin landscape between mouse alpha, beta, and delta cells using ATAC-Seq to evaluate the significant differences in chromatin accessibility. The similarities and differences in chromatin accessibility between these related islet endocrine cells help define their fate in support of their distinct functional roles. We identify patterns that suggest that both alpha and delta cells are poised, but repressed, from becoming beta-like. We also identify patterns in differentially enriched chromatin that have transcription factor motifs preferentially associated with different regions of the genome. Finally, we identify and visualize both novel and previously discovered common endocrine- and cell specific- enhancer regions across differentially enriched chromatin.

scholarly journals High-Throughput Sequencing is a Crucial Tool to Investigate the Contribution of Human Endogenous Retroviruses (HERVs) to Human Biology and Development

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 633 ◽  
Author(s):  
Maria Paola Pisano ◽  
Nicole Grandi ◽  
Enzo Tramontano
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Developmental Stages ◽  
Large Fraction ◽  
Expression Patterns ◽  
Cell Types ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Retroviral Infections ◽  
The Impact

Human Endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that represent a large fraction of our genome. Their transcriptional activity is finely regulated in early developmental stages and their expression is modulated in different cell types and tissues. Such activity has an impact on human physiology and pathology that is only partially understood up to date. Novel high-throughput sequencing tools have recently allowed for a great advancement in elucidating the various HERV expression patterns in different tissues as well as the mechanisms controlling their transcription, and overall, have helped in gaining better insights in an all-inclusive understanding of the impact of HERVs in biology of the host.

miRNA Profiling of Pediatric ALL and Non-Hodgkin Lymphomas.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2719-2719
Author(s):  
Pablo Landgraf ◽  
Amanda Rice ◽  
Nicola Iovino ◽  
Valerio Fulci ◽  
Robert Sheridan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Lines ◽  
Burkitt Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Expression Patterns ◽  
Critical Role ◽  
Mrna Translation ◽  
Cell Types ◽  
Two Samples ◽  
Hematopoetic Stem Cells

Abstract MicroRNAs (miRNAs) are conserved 21−23 nt non-coding RNA molecules that regulate gene expression either by mRNA cleavage or by repression of mRNA translation. miRNAs regulate many different processes, including apoptosis and cell proliferation and may therefore also play a critical role in oncogenic transformation. To date, most miRNAs have been discovered by cDNA cloning and sequencing, though other profiling methods, such as miRNA micro-arrays, have recently been applied. Profiling of miRNA expression by cloning has the advantage of identifying new miRNA genes, and if a large number of clones are sequenced, to also be quantitative. In addition the exact sequence is determined and polymorphisms and mutations in any miRNAs can readily be detected. To get an insight in the role of miRNAs in the differentiation and maturation of hematopoetic cells as well as their contribution to oncogenesis in ALL and lymphomas, we cloned and sequenced various cell lines and patient samples:five cell lines (B-ALL, AML, Burkitt Lymphoma); samples from sorted blood cells covering pluripotent stem cells, B-, T-, NK- cells, monocytes and granulocytes; eight patient samples with ALL (2 pro-B-ALL, 2 pre-B-ALL, 2 cALL, 2 T-ALL) at the time point of diagnosis; four additional samples of these patients with B-ALL and two samples of T-ALL patients each after 36 days of treatment according to the protocol of the German Cooperative Acute Lymphoblastic Leukemia study group (COALL-07-03). We also recorded the small RNA profiles of three patients with various forms of AML at diagnosis and after the first induction according to the protocol of the AML-BFM 2004 study; two Burkitt lymphoma samples and one B-Non Hodgkin Lymphoma (B-NHL) sample. We report here the identification of over 20 novel human miRNAs in these samples. To determine specific expression patterns, the miRNA profiles were compared to a reference set of 22 different human tissue types. Some miRNAs are expressed in a cell or tissue specific manner, others have a more general expression pattern between different cell types and tissues. For example human miRNA miR-142 is ubiquitously expressed in cells of the hematopoetic lineage, whereas human miR-150 is only expressed in differentiated hematopoetic cells, but not in hematopoetic stem cells. In hematopoetic stem cells human miR-126 is 3 to more than 10 times higher expressed than in differentiated hematopoetic cells. The existence of the latter two in humans are first described in this study. miR-16 on the other hand is expressed in all cell types examined including non-hematopoetic. Furthermore, miRNAs are up/down-regulated in ALL and NHL patient samples. In conclusion, this study identifies miRNAs that might be involved in hematopoetic cell differentiation and maturation and is important to identify miRNAs that might contribute to oncogenesis in leukemia and lymphomas.

scholarly journals Systematic clustering algorithm for chromatin accessibility data and its application to hematopoietic cells

2020 ◽  
Vol 16 (11) ◽  
pp. e1008422
Author(s):  
Azusa Tanaka ◽  
Yasuhiro Ishitsuka ◽  
Hiroki Ohta ◽  
Akihiro Fujimoto ◽  
Jun-ichirou Yasunaga ◽  
...  
Keyword(s):  
Data Reduction ◽  
Clustering Algorithm ◽  
High Throughput Sequencing ◽  
Hematopoietic Cells ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Open Chromatin ◽  
Genome Wide ◽  
Data Reduction Method ◽  
Effective Analysis

The huge amount of data acquired by high-throughput sequencing requires data reduction for effective analysis. Here we give a clustering algorithm for genome-wide open chromatin data using a new data reduction method. This method regards the genome as a string of 1s and 0s based on a set of peaks and calculates the Hamming distances between the strings. This algorithm with the systematically optimized set of peaks enables us to quantitatively evaluate differences between samples of hematopoietic cells and classify cell types, potentially leading to a better understanding of leukemia pathogenesis.

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.

scholarly journals Comprehensive integration of single cell data

2018 ◽  
Author(s):  
Tim Stuart ◽  
Andrew Butler ◽  
Paul Hoffman ◽  
Christoph Hafemeister ◽  
Efthymia Papalexi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Expression Patterns ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Substantial Improvement ◽  
Single Cell Protein ◽  
Cell Protein ◽  
Spatial Positioning ◽  
Cell Data

Single cell transcriptomics (scRNA-seq) has transformed our ability to discover and annotate cell types and states, but deep biological understanding requires more than a taxonomic listing of clusters. As new methods arise to measure distinct cellular modalities, including high-dimensional immunophenotypes, chromatin accessibility, and spatial positioning, a key analytical challenge is to integrate these datasets into a harmonized atlas that can be used to better understand cellular identity and function. Here, we develop a computational strategy to “anchor” diverse datasets together, enabling us to integrate and compare single cell measurements not only across scRNA-seq technologies, but different modalities as well. After demonstrating substantial improvement over existing methods for data integration, we anchor scRNA-seq experiments with scATAC-seq datasets to explore chromatin differences in closely related interneuron subsets, and project single cell protein measurements onto a human bone marrow atlas to annotate and characterize lymphocyte populations. Lastly, we demonstrate how anchoring can harmonize in-situ gene expression and scRNA-seq datasets, allowing for the transcriptome-wide imputation of spatial gene expression patterns, and the identification of spatial relationships between mapped cell types in the visual cortex. Our work presents a strategy for comprehensive integration of single cell data, including the assembly of harmonized references, and the transfer of information across datasets.Availability: Installation instructions, documentation, and tutorials are available at: https://www.satijalab.org/seurat

scholarly journals Comprehensive characterization of tissue-specific chromatin accessibility in L2 Caenorhabditis elegans nematodes

2020 ◽  
Author(s):  
Timothy J. Durham ◽  
Riza M. Daza ◽  
Louis Gevirtzman ◽  
Darren A. Cusanovich ◽  
William Stafford Noble ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Expression Patterns ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Gene Expression Patterns ◽  
Rna Seq ◽  
Cell Type ◽  
Tissue Specific ◽  
C Elegans

AbstractRecently developed single cell technologies allow researchers to characterize cell states at ever greater resolution and scale. C. elegans is a particularly tractable system for studying development, and recent single cell RNA-seq studies characterized the gene expression patterns for nearly every cell type in the embryo and at the second larval stage (L2). Gene expression patterns are useful for learning about gene function and give insight into the biochemical state of different cell types; however, in order to understand these cell types, we must also determine how these gene expression levels are regulated. We present the first single cell ATAC-seq study in C. elegans. We collected data in L2 larvae to match the available single cell RNA-seq data set, and we identify tissue-specific chromatin accessibility patterns that align well with existing data, including the L2 single cell RNA-seq results. Using a novel implementation of the latent Dirichlet allocation algorithm, we leverage the single-cell resolution of the sci-ATAC-seq data to identify accessible loci at the level of individual cell types, providing new maps of putative cell type-specific gene regulatory sites, with promise for better understanding of cellular differentiation and gene regulation in the worm.

scholarly journals Layer-specific chromatin accessibility landscapes reveal regulatory networks in adult mouse visual cortex

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Lucas T Gray ◽  
Zizhen Yao ◽  
Thuc Nghi Nguyen ◽  
Tae Kyung Kim ◽  
Hongkui Zeng ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Regulatory Networks ◽  
High Throughput Sequencing ◽  
Adult Mouse ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Binding Motifs ◽  
Mouse Cortex ◽  
Mouse Visual Cortex

Mammalian cortex is a laminar structure, with each layer composed of a characteristic set of cell types with different morphological, electrophysiological, and connectional properties. Here, we define chromatin accessibility landscapes of major, layer-specific excitatory classes of neurons, and compare them to each other and to inhibitory cortical neurons using the Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq). We identify a large number of layer-specific accessible sites, and significant association with genes that are expressed in specific cortical layers. Integration of these data with layer-specific transcriptomic profiles and transcription factor binding motifs enabled us to construct a regulatory network revealing potential key layer-specific regulators, including Cux1/2, Foxp2, Nfia, Pou3f2, and Rorb. This dataset is a valuable resource for identifying candidate layer-specific cis-regulatory elements in adult mouse cortex.

scholarly journals Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease.

1996 ◽  
Vol 183 (3) ◽  
pp. 847-856 ◽  
Author(s):  
A Mizoguchi ◽  
E Mizoguchi ◽  
C Chiba ◽  
G M Spiekermann ◽  
S Tonegawa ◽  
...  
Keyword(s):  
B Cells ◽  
Beta Cells ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Gamma Delta ◽  
Ifn Gamma ◽  
Inflammatory Bowel ◽  
Alpha Beta ◽  
Delta Cells ◽  
Cytokine Imbalance

Spontaneous inflammatory bowel disease (IBD) resembling human ulcerative colitis develops in mice mutant for the T cell receptor alpha gene (TCR-alpha-/-). TCR-alpha-/- mice lack TCR-alpha/beta+ cells but contain TCR-gamma/delta+ cells and a small population of a unique CD4+, TCR-alpha-/beta+(low) cells. Since all the immunoglobulin (Ig) classes are present in these mice, help to B cells must be provided by cells other than TCR-alpha/beta+ cells. In the present study, we found serum levels of IgG1 and IgG2 to be markedly increased in TCR-alpha-/- mice with IBD as compared to TCR-alpha-/- mice without IBD or TCR-alpha+/- controls. An increase in IgG1-, IgG2a- and IgA- but not IgM-secreting mesenteric lymph node (MLN) B cells was detected in TCR-alpha-/- mutant mice. There was also a marked increase in MLN B cells secreting autoantibody (IgG) to tropomyosin, a cytoskeletal protein. Examination of the hyperplastic MLN showed a marked increase in the number of B, TCR-delta+, and CD4+ TCR-alpha-/beta+ cells, similar to the cell population observed at the site of colonic inflammation. Analysis of spontaneous cytokine production by MLN cells using an enzyme-linked immunospot assay, immunohistochemistry, and reverse transcription/polymerase chain reaction showed a decrease of interleukin 2 (IL-2) but a marked increase of IL-4 and interferon gamma (IFN-gamma) production in TCR-alpha-/- mice with IBD as compared to TCR-alpha-/- mice without IBD and TCR alpha+/- control mice. Both TCR-alpha-/beta+ and TCR-delta+ cells were found to be capable of producing IL-4; IFN-gamma was produced mostly by non-T cells, many of which were shown to be CD3- NK 1.1+ cells. We propose that the cytokine imbalance present in these mice results in expansion of B cells, production and switching of autoantibodies to IgG2 subclass, and development of IBD. It is possible that the unusual CD4+ TCR-alpha-/beta+ population and expanded TCR-gamma/delta+ population present in TCR-alpha-/- mice plays a central role in this abnormal immune response.

scholarly journals The pancreatic beta cell: an intricate relation between anatomical structure, the signalling mechanism of glucose-induced insulin secretion, the low antioxidative defence, the high vulnerability and sensitivity to diabetic stress

ChemTexts ◽  
2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Sigurd Lenzen
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Islet Cell ◽  
Pancreatic Beta Cell ◽  
Cell Types ◽  
Antioxidative Defence ◽  
Islet Cell Types ◽  
Low Expression

AbstractThe biosynthesis of insulin takes place in the insulin-producing beta cells that are organized in the form of islets of Langerhans together with a few other islet cell types in the pancreas organ. The signal for glucose-induced insulin secretion is generated in two pathways in the mitochondrial metabolism of the pancreatic beta cells. These pathways are also known as the triggering pathway and the amplifying pathway. Glucokinase, the low-affinity glucose-phosphorylating enzyme in beta cell glycolysis acts as the signal-generating enzyme in this process. ATP ultimately generated is the crucial second messenger in this process. Insulin-producing pancreatic beta cells are badly protected against oxidative stress resulting in a particular vulnerability of this islet cell type due to low expression of H2O2-inactivating enzymes in various subcellular locations, specifically in the cytosol, mitochondria, peroxisomes and endoplasmic reticulum. This is in contrast to the glucagon-producing alpha cells and other islet cell types in the islets that are well equipped with these H2O2-inactivating enzymes. On the other hand the membranes of the pancreatic beta cells are well protected against lipid peroxidation and ferroptosis through high level expression of glutathione peroxidase 4 (GPx4) and this again is at variance from the situation in the non-beta cells of the islets with a low expression level of GPx4. The weak antioxidative defence equipment of the pancreatic beta cells, in particular in states of disease, is very dangerous because the resulting particular vulnerability endangers the functionality of the beta cells, making people prone to the development of a diabetic metabolic state.

Mesonephric cell migration induces testis cord formation and Sertoli cell differentiation in the mammalian gonad

Development ◽  
1999 ◽  
Vol 126 (13) ◽  
pp. 2883-2890 ◽  
Author(s):  
C. Tilmann ◽  
B. Capel
Keyword(s):  
Gene Expression ◽  
Cell Migration ◽  
Single Gene ◽  
Expression Patterns ◽  
Critical Role ◽  
Cell Types ◽  
Specific Gene ◽  
Specific Gene Expression ◽  
Male Specific ◽  
Testis Cord

In mammals a single gene on the Y chromosome, Sry, controls testis formation. One of the earliest effects of Sry expression is the induction of somatic cell migration from the mesonephros into the XY gonad. Here we show that mesonephric cells are required for cord formation and male-specific gene expression in XY gonads in a stage-specific manner. Culturing XX gonads with an XY gonad at their surface, as a ‘sandwich’, resulted in cell migration into the XX tissue. Analysis of sandwich gonads revealed that in the presence of migrating cells, XX gonads organized cord structures and acquired male-specific gene expression patterns. From these results, we conclude that mesonephric cell migration plays a critical role in the formation of testis cords and the differentiation of XY versus XX cell types.

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