scholarly journals Human Endogenous Retroviral Long Terminal Repeat Sequences as Cell Type-Specific Promoters in Retroviral Vectors

2009 ◽  
Vol 83 (23) ◽  
pp. 12643-12650 ◽  
Author(s):  
Ulrike Schön ◽  
Olivia Diem ◽  
Laura Leitner ◽  
Walter H. Günzburg ◽  
Dixie L. Mager ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Leukemia Virus ◽  
Cell Types ◽  
Retroviral Vectors ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Cell Type ◽  
Specific Expression ◽  
Hybrid Vectors ◽  
Cell Type Specific

ABSTRACT The human genome contains more than half a million human endogenous retrovirus (HERV) long terminal repeats (LTRs) that can be regarded as mobile regulatory modules. Many of these HERV LTRs have been recruited during evolution as transcriptional control elements for cellular gene expression. We have cloned LTR sequences from two HERV families, HERV-H and HERV-L, differing widely in their activity and tissue specificity into a murine leukemia virus (MLV)-based promoter conversion vector (ProCon). Various human cell lines were infected with the HERV-MLV hybrid vectors, and cell type-specific expression of the reporter gene was compared with the promoter specificity of the corresponding HERV LTRs in transient-transfection assays. Transcription start site analysis of HERV-MLV hybrid vectors revealed preferential use of the HERV promoter initiation site. Our data show that HERV LTRs function in the context of retroviral vectors in certain cell types and have the potential to be useful as cell type-specific promoters in vector construction.

scholarly journals Cell-type Specific Expression Quantitative Trait Loci Associated with Alzheimer Disease in Blood and Brain Tissue

2020 ◽  
Author(s):  
Devanshi Patel ◽  
Xiaoling Zhang ◽  
John J. Farrell ◽  
Jaeyoon Chung ◽  
Thor D. Stein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Eqtl Analysis ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTBecause regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell-types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5,257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1Mb of genes was evaluated using linear regression models for unrelated subjects and linear mixed models for related subjects. Cell type-specific eQTL (ct-eQTL) models included an interaction term for expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2,533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell-types is supported by the observation that a large portion of GWS ct-eQTLs map within 1Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type specific analysis.

scholarly journals Single-cell RNA-sequencing reveals thoracolumbar vertebra heterogeneity and rib-genesis in pigs

2021 ◽  
Author(s):  
Jianbo Li ◽  
Ligang Wang ◽  
Dawei Yu ◽  
Junfeng Hao ◽  
Longchao Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Lumbar Vertebra ◽  
Cell Types ◽  
Cell Type ◽  
Specific Expression ◽  
Coupled Process ◽  
Gene Expression Dynamics ◽  
Cell Type Specific ◽  
Thoracolumbar Vertebra

Thoracolumbar vertebra (TLV) and rib primordium (RP) development is a common evolutionary feature across vertebrates although whole-organism analysis of TLV and RP gene expression dynamics has been lacking. Here we investigated the single-cell transcriptomic landscape of thoracic vertebra (TV), lumbar vertebra (LV), and RP cells from a pig embryo at 27 days post-fertilization (dpf) and identified six cell types with distinct gene-expression signatures. In-depth dissection of the gene-expression dynamics and RNA velocity revealed a coupled process of osteogenesis and angiogenesis during TLV and rib development. Further analysis of cell-type-specific and strand-specific expression uncovered the extremely high levels of HOXA10 3'-UTR sequence specific to osteoblast of LV cells, which may function as anti-HOXA10-antisense by counteracting the HOXA10-antisense effect to determine TLV transition. Thus, this work provides a valuable resource for understanding embryonic osteogenesis and angiogenesis underlying vertebrate TLV and RP development at the cell-type-specific resolution, which serves as a comprehensive view on the transcriptional profile of animal embryo development.

scholarly journals Dynamics of gene expression in single root cells ofA. thaliana

2018 ◽  
Author(s):  
Ken Jean-Baptiste ◽  
José L. McFaline-Figueroa ◽  
Cristina M. Alexandre ◽  
Michael W. Dorrity ◽  
Lauren Saunders ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Developmental Trajectories ◽  
Cell Types ◽  
Cell Type ◽  
Specific Expression ◽  
Root Cells ◽  
Cell Lineages ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTSingle-cell RNA-seq can yield high-resolution cell-type-specific expression signatures that reveal new cell types and the developmental trajectories of cell lineages. Here, we apply this approach toA. thalianaroot cells to capture gene expression in 3,121 root cells. We analyze these data with Monocle 3, which orders single cell transcriptomes in an unsupervised manner and uses machine learning to reconstruct single-cell developmental trajectories along pseudotime. We identify hundreds of genes with cell-type-specific expression, with pseudotime analysis of several cell lineages revealing both known and novel genes that are expressed along a developmental trajectory. We identify transcription factor motifs that are enriched in early and late cells, together with the corresponding candidate transcription factors that likely drive the observed expression patterns. We assess and interpret changes in total RNA expression along developmental trajectories and show that trajectory branch points mark developmental decisions. Finally, by applying heat stress to whole seedlings, we address the longstanding question of possible heterogeneity among cell types in the response to an abiotic stress. Although the response of canonical heat shock genes dominates expression across cell types, subtle but significant differences in other genes can be detected among cell types. Taken together, our results demonstrate that single-cell transcriptomics holds promise for studying plant development and plant physiology with unprecedented resolution.

scholarly journals Cell type-specific biotin labeling in vivo resolves regional neuronal proteomic differences in mouse brain

2021 ◽  
Author(s):  
Sruti Rayaprolu ◽  
Sara Bitarafan ◽  
Ranjita Betarbet ◽  
Sydney N Sunna ◽  
Lihong Cheng ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Neurological Diseases ◽  
Neuronal Cell ◽  
Cell Types ◽  
Proteomic Profiling ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific ◽  
The Brain

Isolation and proteomic profiling of brain cell types, particularly neurons, pose several technical challenges which limit our ability to resolve distinct cellular phenotypes in neurological diseases. Therefore, we generated a novel mouse line that enables cell type-specific expression of a biotin ligase, TurboID, via Cre-lox strategy for in vivo proximity-dependent biotinylation of proteins. Using adenoviral-based and transgenic approaches, we show striking protein biotinylation in neuronal cell bodies and axons throughout the mouse brain. We quantified more than 2,000 neuron-derived proteins following enrichment that mapped to numerous subcellular compartments. Synaptic, transmembrane transporters, ion channel subunits, and disease-relevant druggable targets were among the most significantly enriched proteins. Remarkably, we resolved brain region-specific proteomic profiles of Camk2a neurons with distinct functional molecular signatures and disease associations that may underlie regional neuronal vulnerability. Leveraging the neuronal specificity of this in vivo biotinylation strategy, we used an antibody-based approach to uncover regionally unique patterns of neuron-derived signaling phospho-proteins and cytokines, particularly in the cortex and cerebellum. Our work provides a proteomic framework to investigate cell type-specific mechanisms driving physiological and pathological states of the brain as well as complex tissues beyond the brain.

scholarly journals Super interactive promoters provide insight into cell type-specific regulatory networks in blood lineage cell types

2021 ◽  
Author(s):  
Taylor M. Lagler ◽  
Yuchen Yang ◽  
Yuriko Harigaya ◽  
Vijay G. Sankaran ◽  
Ming Hu ◽  
...  
Keyword(s):  
Blood Cell ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Spatial Organization ◽  
Cell Types ◽  
Gene Promoters ◽  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Insight Into

Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-specific manner for blood lineage cell types. In this study, we leverage promoter capture Hi-C data across a compendium of blood lineage cell types to identify and characterize cell type-specific super-interactive promoters (SIPs). Notably, promoter-interacting regions (PIRs) of SIPs are more likely to overlap with cell type-specific ATAC-seq peaks and GWAS variants for relevant blood cell traits than PIRs of non-SIPs. Further, SIP genes tend to express at a higher level in the corresponding cell type, and show enriched heritability of relevant blood cell trait(s). Importantly, this analysis shows the potential of using promoter-centric analyses of chromatin spatial organization data to identify biologically important genes and their regulatory regions.

scholarly journals Cell-Type Specific Analysis of Selenium-Related Genes in Brain

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 120
Author(s):  
Alexandru R. Sasuclark ◽  
Vedbar S. Khadka ◽  
Matthew W. Pitts
Keyword(s):  
Neural Development ◽  
Cortical Neurons ◽  
Cell Types ◽  
Inhibitory Neurons ◽  
Brain Atlas ◽  
Cell Type ◽  
Specific Expression ◽  
Rnaseq Data ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

Selenoproteins are a unique class of proteins that play key roles in redox signaling in the brain. This unique organ is comprised of a wide variety of cell types that includes excitatory neurons, inhibitory neurons, astrocytes, microglia, and oligodendrocytes. Whereas selenoproteins are known to be required for neural development and function, the cell-type specific expression of selenoproteins and selenium-related machinery has yet to be systematically investigated. Due to advances in sequencing technology and investment from the National Institutes of Health (NIH)-sponsored BRAIN initiative, RNA sequencing (RNAseq) data from thousands of cortical neurons can now be freely accessed and searched using the online RNAseq data navigator at the Allen Brain Atlas. Hence, we utilized this newly developed tool to perform a comprehensive analysis of the cell-type specific expression of selenium-related genes in brain. Select proteins of interest were further verified by means of multi-label immunofluorescent labeling of mouse brain sections. Of potential significance to neural selenium homeostasis, we report co-expression of selenoprotein P (SELENOP) and selenium binding protein 1 (SELENBP1) within astrocytes. These findings raise the intriguing possibility that SELENBP1 may negatively regulate astrocytic SELENOP synthesis and thereby limit downstream Se supply to neurons.

scholarly journals Single-Cell Regulatory Network Inference and Clustering Identifies Cell-Type Specific Expression Pattern of Transcription Factors in Mouse Sciatic Nerve

2021 ◽  
Vol 15 ◽  
Author(s):  
Mingchao Li ◽  
Qing Min ◽  
Matthew C. Banton ◽  
Xinpeng Dun
Keyword(s):  
Transcription Factors ◽  
Sciatic Nerve ◽  
Single Cell ◽  
Cell Types ◽  
Cell Type ◽  
Specific Expression ◽  
Single Cell Rna Sequencing ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Different Cell Types

Advances in single-cell RNA sequencing technologies and bioinformatics methods allow for both the identification of cell types in a complex tissue and the large-scale gene expression profiling of various cell types in a mixture. In this report, we analyzed a single-cell RNA sequencing (scRNA-seq) dataset for the intact adult mouse sciatic nerve and examined cell-type specific transcription factor expression and activity during peripheral nerve homeostasis. In total, we identified 238 transcription factors expressed in nine different cell types of intact mouse sciatic nerve. Vascular smooth muscle cells have the lowest number of transcription factors expressed with 17 transcription factors identified. Myelinating Schwann cells (mSCs) have the highest number of transcription factors expressed, with 61 transcription factors identified. We created a cell-type specific expression map for the identified 238 transcription factors. Our results not only provide valuable information about the expression pattern of transcription factors in different cell types of adult peripheral nerves but also facilitate future studies to understand the function of key transcription factors in the peripheral nerve homeostasis and disease.

scholarly journals Genomics at cellular resolution: insights into cognitive disorders and their evolution

2020 ◽  
Vol 29 (R1) ◽  
pp. R1-R9
Author(s):  
Stefano Berto ◽  
Yuxiang Liu ◽  
Genevieve Konopka
Keyword(s):  
Cognitive Disorders ◽  
Brain Evolution ◽  
Cell Types ◽  
Autism Spectrum ◽  
Specific Cell ◽  
Cell Type ◽  
Specific Expression ◽  
Variant Information ◽  
Cell Type Specific ◽  
And Function

Abstract High-throughput genomic sequencing approaches have held the promise of understanding and ultimately leading to treatments for cognitive disorders such as autism spectrum disorders, schizophrenia and Alzheimer’s disease. Although significant progress has been made into identifying genetic variants associated with these diseases, these studies have also uncovered that these disorders are mostly genetically complex and thus challenging to model in non-human systems. Improvements in such models might benefit from understanding the evolution of the human genome and how such modifications have affected brain development and function. The intersection of genome-wide variant information with cell-type-specific expression and epigenetic information will further assist in resolving the contribution of particular cell types in evolution or disease. For example, the role of non-neuronal cells in brain evolution and cognitive disorders has gone mostly underappreciated until the recent availability of single-cell transcriptomic approaches. In this review, we discuss recent studies that carry out cell-type-specific assessments of gene expression in brain tissue across primates and between healthy and disease populations. The emerging results from these studies are beginning to elucidate how specific cell types in the evolved human brain are contributing to cognitive disorders.

scholarly journals Detection of allele-specific expression in spatial transcriptomics with spASE

2021 ◽  
Author(s):  
Luli S. Zou ◽  
Tongtong Zhao ◽  
Dylan M. Cable ◽  
Evan Murray ◽  
Martin J. Aryee ◽  
...  
Keyword(s):  
Statistical Power ◽  
Cell Types ◽  
Cell Type ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Preferential Expression ◽  
Mouse Hippocampus ◽  
Transcriptomics Data ◽  
Allele Specific ◽  
Cell Type Specific

AbstractAllele-specific expression (ASE), or the preferential expression of one allele, can be observed in transcriptomics data from early development throughout the lifespan. However, the prevalence of spatial and cell type-specific ASE variation remains unclear. Spatial transcriptomics technologies permit the study of spatial ASE patterns genome-wide at near-single-cell resolution. However, the data are highly sparse, and confounding between cell type and spatial location present further statistical challenges. Here, we introduce spASE (https://github.com/lulizou/spase), a computational framework for detecting spatial patterns in ASE within and across cell types from spatial transcriptomics data. To tackle the challenge presented by the low signal to noise ratio due to the sparsity of the data, we implement a spatial smoothing approach that greatly improves statistical power. We generated Slide-seqV2 data from the mouse hippocampus and detected ASE in X-chromosome genes, both within and across cell type, validating our ability to recover known ASE patterns. We demonstrate that our method can also identify cell type-specific effects, which we find can explain the majority of the spatial signal for autosomal genes. The findings facilitated by our method provide new insight into the uncharacterized landscape of spatial and cell type-specific ASE in the mouse hippocampus.

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