scholarly journals Spatiotemporal transcriptomics reveals pathogenesis of viral myocarditis

2021 ◽  
Author(s):  
Madhav Mantri ◽  
Meleana M. Hinchman ◽  
David W. McKellar ◽  
Michael F. Z. Wang ◽  
Shaun T. Cross ◽  
...  
Keyword(s):  
Stress Responses ◽  
Cytotoxic T Cells ◽  
Viral Myocarditis ◽  
Cardiac Cells ◽  
Cellular Heterogeneity ◽  
Border Zone ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Reovirus Infection ◽  
Molecular Events

A significant fraction of sudden death in children and young adults is due to myocarditis, an inflammatory disease of the heart, most often caused by viral infection. Here we used integrated single-cell and spatial transcriptomics to create a high-resolution, spatially resolved map of reovirus-induced myocarditis in neonatal murine hearts. We assayed hearts collected at three timepoints after reovirus infection and studied the temporal, spatial, and cellular heterogeneity of host-virus interactions. We further assayed the intestine, the primary site of reovirus infection to establish a full chronology of molecular events that ultimately lead to myocarditis. We implemented targeted enrichment of viral transcripts to establish the cellular targets of the virus in the intestine and the heart. Our data give insight into the cell-type specificity of innate immune responses, and into the transcriptional states of inflamed cardiac cells that recruit circulating immune cells, including cytotoxic T cells which induce pyroptosis in the myocarditic tissue. Analyses of spatially restricted gene expression in myocarditic regions and the border zone around those regions identified immune-mediated cell-type specific injury and stress responses. Overall, we observe a dynamic and complex network of cellular phenotypes and cell-cell interactions associated with viral myocarditis.

scholarly journals GeneMarkeR: A Database and User Interface for scRNA-seq Marker Genes

2021 ◽  
Vol 12 ◽  
Author(s):  
Brianna M. Paisley ◽  
Yunlong Liu
Keyword(s):  
Marker Gene ◽  
Cell Types ◽  
Cellular Heterogeneity ◽  
Marker Genes ◽  
Cell Type ◽  
Web Tool ◽  
Cell Type Specificity ◽  
Public Data ◽  
R Shiny ◽  
Unique Cell

Single-cell sequencing (scRNA-seq) has enabled researchers to study cellular heterogeneity. Accurate cell type identification is crucial for scRNA-seq analysis to be valid and robust. Marker genes, genes specific for one or a few cell types, can improve cell type classification; however, their specificity varies across species, samples, and cell subtypes. Current marker gene databases lack standardization, cell hierarchy consideration, sample diversity, and/or the flexibility for updates as new data become available. Most of these databases are derived from a single statistical analysis despite many such analyses scattered in the literature to identify marker genes from scRNA-seq data and pure cell populations. An R Shiny web tool called GeneMarkeR was developed for researchers to retrieve marker genes demonstrating cell type specificity across species, methodology and sample types based on a novel algorithm. The web tool facilitates online submission and interfaces with MySQL to ensure updatability. Furthermore, the tool incorporates reactive programming to enable researchers to retrieve standardized public data supporting the marker genes. GeneMarkeR currently hosts over 261,000 rows of standardized marker gene results from 25 studies across 21,012 unique genomic entities and 99 unique cell types mapped to hierarchical ontologies.

scholarly journals Comprehensive analysis of single cell ATAC-seq data with SnapATAC

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rongxin Fang ◽  
Sebastian Preissl ◽  
Yang Li ◽  
Xiaomeng Hou ◽  
Jacinta Lucero ◽  
...  
Keyword(s):  
Single Cell ◽  
Single Cell Analysis ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Cellular Heterogeneity ◽  
Specific Gene ◽  
Open Chromatin ◽  
Cell Type ◽  
Process Data ◽  
Cell Type Specific

AbstractIdentification of the cis-regulatory elements controlling cell-type specific gene expression patterns is essential for understanding the origin of cellular diversity. Conventional assays to map regulatory elements via open chromatin analysis of primary tissues is hindered by sample heterogeneity. Single cell analysis of accessible chromatin (scATAC-seq) can overcome this limitation. However, the high-level noise of each single cell profile and the large volume of data pose unique computational challenges. Here, we introduce SnapATAC, a software package for analyzing scATAC-seq datasets. SnapATAC dissects cellular heterogeneity in an unbiased manner and map the trajectories of cellular states. Using the Nyström method, SnapATAC can process data from up to a million cells. Furthermore, SnapATAC incorporates existing tools into a comprehensive package for analyzing single cell ATAC-seq dataset. As demonstration of its utility, SnapATAC is applied to 55,592 single-nucleus ATAC-seq profiles from the mouse secondary motor cortex. The analysis reveals ~370,000 candidate regulatory elements in 31 distinct cell populations in this brain region and inferred candidate cell-type specific transcriptional regulators.

scholarly journals Antagonising Chromatin Remodelling Activities in the Regulation of Mammalian Ribosomal Transcription

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 961
Author(s):  
Kanwal Tariq ◽  
Ann-Kristin Östlund Farrants
Keyword(s):  
Stress Responses ◽  
Ribosomal Gene ◽  
Chromatin Remodelling ◽  
Chromatin State ◽  
Rrna Gene ◽  
Open Chromatin ◽  
Histone Chaperones ◽  
Embryonic Cells ◽  
Cell Type ◽  
Chromatin States

Ribosomal transcription constitutes the major energy consuming process in cells and is regulated in response to proliferation, differentiation and metabolic conditions by several signalling pathways. These act on the transcription machinery but also on chromatin factors and ncRNA. The many ribosomal gene repeats are organised in a number of different chromatin states; active, poised, pseudosilent and repressed gene repeats. Some of these chromatin states are unique to the 47rRNA gene repeat and do not occur at other locations in the genome, such as the active state organised with the HMG protein UBF whereas other chromatin state are nucleosomal, harbouring both active and inactive histone marks. The number of repeats in a certain state varies on developmental stage and cell type; embryonic cells have more rRNA gene repeats organised in an open chromatin state, which is replaced by heterochromatin during differentiation, establishing different states depending on cell type. The 47S rRNA gene transcription is regulated in different ways depending on stimulus and chromatin state of individual gene repeats. This review will discuss the present knowledge about factors involved, such as chromatin remodelling factors NuRD, NoRC, CSB, B-WICH, histone modifying enzymes and histone chaperones, in altering gene expression and switching chromatin states in proliferation, differentiation, metabolic changes and stress responses.

scholarly journals Cell-Type Specificity of the Expression of Os BOR1, a Rice Efflux Boron Transporter Gene, Is Regulated in Response to Boron Availability for Efficient Boron Uptake and Xylem Loading

2007 ◽  
Vol 19 (8) ◽  
pp. 2624-2635 ◽  
Author(s):  
Yuko Nakagawa ◽  
Hideki Hanaoka ◽  
Masaharu Kobayashi ◽  
Kazumaru Miyoshi ◽  
Kyoko Miwa ◽  
...  
Keyword(s):  
Transporter Gene ◽  
Cell Type ◽  
Boron Uptake ◽  
Cell Type Specificity ◽  
Xylem Loading ◽  
Boron Transporter

scholarly journals Differential Role of Basal Keratinocytes in UV-Induced Immunosuppression and Skin Cancer

2006 ◽  
Vol 26 (22) ◽  
pp. 8515-8526 ◽  
Author(s):  
Judith Jans ◽  
George A. Garinis ◽  
Wouter Schul ◽  
Adri van Oudenaren ◽  
Michael Moorhouse ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Biological Effects ◽  
Mouse Skin ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Basal Keratinocytes ◽  
Expression Of Genes ◽  
Pyrimidine Dimers ◽  
Response To Stress

ABSTRACT Cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs) comprise major UV-induced photolesions. If left unrepaired, these lesions can induce mutations and skin cancer, which is facilitated by UV-induced immunosuppression. Yet the contribution of lesion and cell type specificity to the harmful biological effects of UV exposure remains currently unclear. Using a series of photolyase-transgenic mice to ubiquitously remove either CPDs or 6-4PPs from all cells in the mouse skin or selectively from basal keratinocytes, we show that the majority of UV-induced acute effects to require the presence of CPDs in basal keratinocytes in the mouse skin. At the fundamental level of gene expression, CPDs induce the expression of genes associated with repair and recombinational processing of DNA damage, as well as apoptosis and a response to stress. At the organismal level, photolyase-mediated removal of CPDs, but not 6-4PPs, from the genome of only basal keratinocytes substantially diminishes the incidence of skin tumors; however, it does not affect the UVB-mediated immunosuppression. Taken together, these findings reveal a differential role of basal keratinocytes in these processes, providing novel insights into the skin's acute and chronic responses to UV in a lesion- and cell-type-specific manner.

scholarly journals Tissue-Specific Transcriptional Targeting of a Replication-Competent Retroviral Vector

2002 ◽  
Vol 76 (24) ◽  
pp. 12783-12791 ◽  
Author(s):  
Christopher R. Logg ◽  
Aki Logg ◽  
Robert J. Matusik ◽  
Bernard H. Bochner ◽  
Noriyuki Kasahara
Keyword(s):  
Tumor Cells ◽  
Viral Vectors ◽  
High Efficiency ◽  
Leukemia Virus ◽  
Transduction Efficiency ◽  
Promoter Strength ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Tissue Specific

ABSTRACT The inability of replication-defective viral vectors to efficiently transduce tumor cells in vivo has prevented the successful application of such vectors in gene therapy of cancer. To address the need for more efficient gene delivery systems, we have developed replication-competent retroviral (RCR) vectors based on murine leukemia virus (MLV). We have previously shown that such vectors are capable of transducing solid tumors in vivo with very high efficiency. While the natural requirement of MLV infection for cell division imparts a certain degree of specificity for tumor cells, additional means for confining RCR vector replication to tumor cells are desirable. Here, we investigated the parameters critical for successful tissue-specific transcriptional control of RCR vector replication by replacing various lengths of the MLV enhancer/promoter with sequences derived either from the highly prostate-specific probasin (PB) promoter or from a more potent synthetic variant of the PB promoter. We assessed the transcriptional specificity of the resulting hybrid long terminal repeats (LTRs) and the cell type specificity and efficiency of replication of vectors containing these LTRs. Incorporation of PB promoter sequences effectively restricted transcription from the LTR to prostate-derived cells and imparted prostate-specific RCR vector replication but required the stronger synthetic promoter and retention of native MLV sequences in the vicinity of the TATA box for optimal replicative efficiency and specificity. Our results have thus identified promoter strength and positioning within the LTR as important determinants for achieving both high transduction efficiency and strict cell type specificity in transcriptionally targeted RCR vectors.

The retinotectal projections after uncrossing the optic chiasma in Xenopus with one compound eye

Development ◽  
1971 ◽  
Vol 26 (3) ◽  
pp. 523-542
Author(s):  
K. Straznicky ◽  
R. M. Gaze ◽  
M. J. Keating
Keyword(s):  
Compound Eye ◽  
The Other ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Optic Chiasma ◽  
Normal Side ◽  
Cell Specificity ◽  
Normal Projection ◽  
Retinotectal Projections ◽  
Fixed Cell

The nature of the retinotectal projection from a compound (NN or TT) eye in Xenopus raises certain problems concerning the mode of formation of connexions between the eye and the tectum. Each half of the compound eye appears to spread its connexions across the entire extent of the (apparently normal) contralateral tectum. This could indicate a certain plasticity in the way in which optic fibres can connect with the tectum. Alternatively, it is conceivable that each (similar) half of the compound eye is only able to innervate its corresponding half-tectum; in which case the uninnervated half-tectum could remain undeveloped and the innervated half-tectum could overgrow to resemble a normal tectum. This mechanism would preserve the idea of a rigidly fixed cell-to-cell specificity between retina and tectum. In an attempt to distinguish between these two mechanisms (spreading or overgrown half-tectum) we have given each of a series of Xenopus embryos at stage 32 one compound eye (NN or TT). Then, shortly after metamorphosis, we uncrossed the optic chiasma and 6 months later recorded the retinotectal projections from each eye to the tecta. Thus by connecting up the normal eye to the suspect tectum, and the compound eye to the normal tectum, we used the normal side in each case to provide an indication of the degree of abnormality with which the other side was connected. The results showed that a compound eye (NN or TT), connected to a normal tectum, gave a typical reduplicated map across the entire tectum, whereas the normal eye, when connected to the tectum which was previously innervated by the compound eye, gave an approximately normal projection across the whole of that tectum. These results lead us to conclude that, in the Xenopus visual system, no strict cell-to-cell type specificity exists; rather, what is preserved throughout these experimental manoeuvres is the polarity and extent of the projection.

Sign in / Sign up

Export Citation Format

Share Document