scholarly journals Genome-wide expression of the residual lung reacting to experimental Pneumonectomy

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Valerio Napolioni ◽  
Fortunato Bianconi ◽  
Rossella Potenza ◽  
Francesco M. Carpi ◽  
Vienna Ludovini ◽  
...  
Keyword(s):  
Gene Networks ◽  
Expression Patterns ◽  
Specific Gene ◽  
Swine Model ◽  
Rna Seq ◽  
Network Analyses ◽  
Genome Wide ◽  
Significant Enrichment ◽  
Transcriptome Expression ◽  
Left Pneumonectomy

Abstract Background Acute or chronic irreversible respiratory failure may occur in patients undergoing pneumonectomy. Aim of this study was to determine transcriptome expression changes after experimental pneumonectomy in swine model. Experimental left pneumonectomy was performed in five pigs under general anaesthesia. Both the resected and the remaining lung, after 60 post-operative completely uneventful days, underwent genome-wide bulk RNA-Sequencing (RNA-Seq). Results Histological analysis showed dilation of air spaces and rupture of interalveolar septa. In addition, mild inflammation, no fibrosis, radial stretch of the bronchus, strong enlargement of airspaces and thinning of the blood supply were observed. Bioinformatic analyses of bulk RNA-Seq data identified 553 Differentially Expressed Genes (DEGs) at adjusted P-value below 0.001, between pre- and post-pneumonectomy. The top 10 up-regulated DEGs were Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; the top 10 down-regulated DEGs were Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. Leveraging digital cytometry tools, no difference in cellular abundance was found between the two experimental groups, while the analysis of cell type-specific gene expression patterns highlighted a striking predominance of macrophage-specific genes among the DEGs. DAVID-based gene ontology analysis showed a significant enrichment of “Extrinsic apoptotic signaling pathway” (FDR q = 7.60 × 10− 3) and “Response to insulin” (FDR q = 7.60 × 10− 3) genes, along with an enrichment of genes involved as “Negative regulators of DDX58/IFIH1 signaling” (FDR q = 7.50 × 10− 4) found by querying the REACTOME pathway database. Gene network analyses indicated a general dysregulation of gene inter-connections. Conclusion This translational genomics study highlighted the existence both of individual genes, mostly dysregulated in certain cellular populations (e.g., macrophages), and gene-networks involved in pulmonary reaction after left pneumonectomy. Their involvement in lung homeostasis is largely supported by previous studies, carried out both in humans and in other animal models (under homeostatic or disease-related conditions), that adopted candidate-gene approaches. Overall, the present findings represent a preliminary assessment for future, more focused, studies on compensatory lung adaptation, pulmonary regeneration and functional reload.

scholarly journals Imprinting effects of UBE3A loss on synaptic gene networks and Wnt signaling pathways

2019 ◽  
Vol 28 (22) ◽  
pp. 3842-3852 ◽  
Author(s):  
S Jesse Lopez ◽  
Benjamin I Laufer ◽  
Ulrika Beitnere ◽  
Elizabeth L Berg ◽  
Jill L Silverman ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Gene Networks ◽  
Neurodevelopmental Disorder ◽  
Expression Patterns ◽  
Synaptic Regulation ◽  
Network Analyses ◽  
Ubiquitin E3 Ligase ◽  
Genome Wide ◽  
Genome Bisulfite Sequencing ◽  
Parent Of Origin

Abstract Ubiquitin E3 ligase 3A (UBE3A) encodes an E3 ubiquitin ligase whose loss from the maternal allele causes the neurodevelopmental disorder Angelman syndrome (AS). Previous studies of UBE3A function have not examined full Ube3a deletion in mouse, the complexity of imprinted gene networks in brain nor the molecular basis of systems-level cognitive dysfunctions in AS. We therefore utilized a systems biology approach to elucidate how UBE3A loss impacts the early postnatal brain in a novel CRISPR/Cas9-engineered rat Angelman model of a complete Ube3a deletion. Strand-specific transcriptome analysis of offspring from maternally or paternally inherited Ube3a deletions revealed the expected parental expression patterns of Ube3a sense and antisense transcripts by postnatal day 2 (P2) in hypothalamus and day 9 (P9) in cortex, compared to wild-type littermates. The dependency of genome-wide effects on parent-of-origin, Ube3a genotype and time (P2 and P9) was investigated through transcriptome (RNA sequencing of cortex and hypothalamus) and methylome (whole-genome bisulfite sequencing of hypothalamus). Weighted gene co-expression and co-methylation network analyses identified co-regulated networks in maternally inherited Ube3a deletion offspring enriched in postnatal developmental processes including Wnt signaling, synaptic regulation, neuronal and glial functions, epigenetic regulation, ubiquitin, circadian entrainment and splicing. Furthermore, we showed that loss of the paternal Ube3a antisense transcript resulted in both unique and overlapping dysregulated gene pathways with maternal loss, predominantly at the level of differential methylation. Together, these results provide a holistic examination of the molecular impacts of UBE3A loss in brain, supporting the existence of interactive epigenetic networks between maternal and paternal transcripts at the Ube3a locus.

scholarly journals Genome-wide analysis and expression profile of the bZIP gene family in poplar

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kai Zhao ◽  
Song Chen ◽  
Wenjing Yao ◽  
Zihan Cheng ◽  
Boru Zhou ◽  
...  
Keyword(s):  
Salt Stress ◽  
Systems Biology ◽  
Gene Family ◽  
Stress Responses ◽  
Metal Ion ◽  
Gene Networks ◽  
Expression Patterns ◽  
Gene Set Enrichment Analysis ◽  
Specific Gene ◽  
Biological Processes

Abstract Background The bZIP gene family, which is widely present in plants, participates in varied biological processes including growth and development and stress responses. How do the genes regulate such biological processes? Systems biology is powerful for mechanistic understanding of gene functions. However, such studies have not yet been reported in poplar. Results In this study, we identified 86 poplar bZIP transcription factors and described their conserved domains. According to the results of phylogenetic tree, we divided these members into 12 groups with specific gene structures and motif compositions. The corresponding genes that harbor a large number of segmental duplication events are unevenly distributed on the 17 poplar chromosomes. In addition, we further examined collinearity between these genes and the related genes from six other species. Evidence from transcriptomic data indicated that the bZIP genes in poplar displayed different expression patterns in roots, stems, and leaves. Furthermore, we identified 45 bZIP genes that respond to salt stress in the three tissues. We performed co-expression analysis on the representative genes, followed by gene set enrichment analysis. The results demonstrated that tissue differentially expressed genes, especially the co-expressing genes, are mainly involved in secondary metabolic and secondary metabolite biosynthetic processes. However, salt stress responsive genes and their co-expressing genes mainly participate in the regulation of metal ion transport, and methionine biosynthetic. Conclusions Using comparative genomics and systems biology approaches, we, for the first time, systematically explore the structures and functions of the bZIP gene family in poplar. It appears that the bZIP gene family plays significant roles in regulation of poplar development and growth and salt stress responses through differential gene networks or biological processes. These findings provide the foundation for genetic breeding by engineering target regulators and corresponding gene networks into poplar lines.

scholarly journals Limit cycle dynamics can guide the evolution of gene regulatory networks towards point attractors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stuart P. Wilson ◽  
Sebastian S. James ◽  
Daniel J. Whiteley ◽  
Leah A. Krubitzer
Keyword(s):  
Gene Expression ◽  
Limit Cycles ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Specific Gene ◽  
Boolean Models ◽  
A Genome ◽  
Order Of Magnitude ◽  
Accelerate Evolution

AbstractDevelopmental dynamics in Boolean models of gene networks self-organize, either into point attractors (stable repeating patterns of gene expression) or limit cycles (stable repeating sequences of patterns), depending on the network interactions specified by a genome of evolvable bits. Genome specifications for dynamics that can map specific gene expression patterns in early development onto specific point attractor patterns in later development are essentially impossible to discover by chance mutation alone, even for small networks. We show that selection for approximate mappings, dynamically maintained in the states comprising limit cycles, can accelerate evolution by at least an order of magnitude. These results suggest that self-organizing dynamics that occur within lifetimes can, in principle, guide natural selection across lifetimes.

scholarly journals Integrative genome-wide analysis reveals the role of WIP proteins in inhibition of growth and development

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Maria Victoria Gomez Roldan ◽  
Farhaj Izhaq ◽  
Marion Verdenaud ◽  
John Eleblu ◽  
Aimen Haraghi ◽  
...  
Keyword(s):  
Gene Networks ◽  
Growth Arrest ◽  
Reproductive Organs ◽  
Stress Signaling ◽  
Rna Seq ◽  
Genome Wide Analysis ◽  
Inhibition Of Growth ◽  
Genome Wide ◽  
Male Flowers

AbstractIn cucurbits, CmWIP1 is a master gene controlling sex determination. To bring new insight in the function of CmWIP1, we investigated two Arabidopsis WIP transcription factors, AtWIP1/TT1 and AtWIP2/NTT. Using an inducible system we showed that WIPs are powerful inhibitor of growth and inducer of cell death. Using ChIP-seq and RNA-seq we revealed that most of the up-regulated genes bound by WIPs display a W-box motif, associated with stress signaling. In contrast, the down-regulated genes contain a GAGA motif, a known target of polycomb repressive complex. To validate the role of WIP proteins in inhibition of growth, we expressed AtWIP1/TT1 in carpel primordia and obtained male flowers, mimicking CmWIP1 function in melon. Using other promoters, we further demonstrated that WIPs can trigger growth arrest of both vegetative and reproductive organs. Our data supports an evolutionary conserved role of WIPs in recruiting gene networks controlling growth and adaptation to stress.

scholarly journals Emerging Roles of Estrogen-Regulated Enhancer and Long Non-Coding RNAs

2020 ◽  
Vol 21 (10) ◽  
pp. 3711
Author(s):  
Melina J. Sedano ◽  
Alana L. Harrison ◽  
Mina Zilaie ◽  
Chandrima Das ◽  
Ramesh Choudhari ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Expression Patterns ◽  
Biological Significance ◽  
Rna Seq ◽  
Biological Functions ◽  
Protein Coding ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Non Coding Rnas

Genome-wide RNA sequencing has shown that only a small fraction of the human genome is transcribed into protein-coding mRNAs. While once thought to be “junk” DNA, recent findings indicate that the rest of the genome encodes many types of non-coding RNA molecules with a myriad of functions still being determined. Among the non-coding RNAs, long non-coding RNAs (lncRNA) and enhancer RNAs (eRNA) are found to be most copious. While their exact biological functions and mechanisms of action are currently unknown, technologies such as next-generation RNA sequencing (RNA-seq) and global nuclear run-on sequencing (GRO-seq) have begun deciphering their expression patterns and biological significance. In addition to their identification, it has been shown that the expression of long non-coding RNAs and enhancer RNAs can vary due to spatial, temporal, developmental, or hormonal variations. In this review, we explore newly reported information on estrogen-regulated eRNAs and lncRNAs and their associated biological functions to help outline their markedly prominent roles in estrogen-dependent signaling.

scholarly journals Beyond the ENCODE project: using genomics and epigenomics strategies to study enhancer evolution

2013 ◽  
Vol 368 (1632) ◽  
pp. 20130022 ◽  
Author(s):  
Noboru Jo Sakabe ◽  
Marcelo A. Nobrega
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Expression Patterns ◽  
Dna Interaction ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Genome Wide ◽  
Identify Transcription Factor ◽  
Specific Proteins ◽  
Species Specific

The complex expression patterns observed for many genes are often regulated by distal transcription enhancers. Changes in the nucleotide sequences of enhancers may therefore lead to changes in gene expression, representing a central mechanism by which organisms evolve. With the development of the experimental technique of chromatin immunoprecipitation (ChIP), in which discrete regions of the genome bound by specific proteins can be identified, it is now possible to identify transcription factor binding events (putative cis -regulatory elements) in entire genomes. Comparing protein–DNA binding maps allows us, for the first time, to attempt to identify regulatory differences and infer global patterns of change in gene expression across species. Here, we review studies that used genome-wide ChIP to study the evolution of enhancers. The trend is one of high divergence of cis -regulatory elements between species, possibly compensated by extensive creation and loss of regulatory elements and rewiring of their target genes. We speculate on the meaning of the differences observed and discuss that although ChIP experiments identify the biochemical event of protein–DNA interaction, it cannot determine whether the event results in a biological function, and therefore more studies are required to establish the effect of divergence of binding events on species-specific gene expression.

scholarly journals Transcriptome Analysis in Domesticated Species: Challenges and Strategies

2015 ◽  
Vol 9S4 ◽  
pp. BBI.S29334 ◽  
Author(s):  
Jessica P. Hekman ◽  
Jennifer L Johnson ◽  
Anna V. Kukekova
Keyword(s):  
Complex Traits ◽  
Gene Networks ◽  
Association Studies ◽  
Cultural Value ◽  
Genomic Research ◽  
Model Organisms ◽  
Genome Wide Association Studies ◽  
Rna Seq ◽  
Genome Wide ◽  
Genome Assemblies

Domesticated species occupy a special place in the human world due to their economic and cultural value. In the era of genomic research, domesticated species provide unique advantages for investigation of diseases and complex phenotypes. RNA sequencing, or RNA-seq, has recently emerged as a new approach for studying transcriptional activity of the whole genome, changing the focus from individual genes to gene networks. RNA-seq analysis in domesticated species may complement genome-wide association studies of complex traits with economic importance or direct relevance to biomedical research. However, RNA-seq studies are more challenging in domesticated species than in model organisms. These challenges are at least in part associated with the lack of quality genome assemblies for some domesticated species and the absence of genome assemblies for others. In this review, we discuss strategies for analyzing RNA-seq data, focusing particularly on questions and examples relevant to domesticated species.

scholarly journals Interferon-regulated genetic programs and JAK/STAT pathway activate the intronic promoter of the short ACE2 isoform in renal proximal tubules

2021 ◽  
Author(s):  
Jakub Jankowski ◽  
Hye Kyung Lee ◽  
Julia Wilflingseder ◽  
Lothar Hennighausen
Keyword(s):  
Gene Expression ◽  
Proximal Tubule ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Regulatory Elements ◽  
Rna Seq ◽  
Angiotensin Converting Enzyme 2 ◽  
Genome Wide ◽  
Cytokine Stimulation

SummaryRecently, a short, interferon-inducible isoform of Angiotensin-Converting Enzyme 2 (ACE2), dACE2 was identified. ACE2 is a SARS-Cov-2 receptor and changes in its renal expression have been linked to several human nephropathies. These changes were never analyzed in context of dACE2, as its expression was not investigated in the kidney. We used Human Primary Proximal Tubule (HPPT) cells to show genome-wide gene expression patterns after cytokine stimulation, with emphasis on the ACE2/dACE2 locus. Putative regulatory elements controlling dACE2 expression were identified using ChIP-seq and RNA-seq. qRT-PCR differentiating between ACE2 and dACE2 revealed 300- and 600-fold upregulation of dACE2 by IFNα and IFNβ, respectively, while full length ACE2 expression was almost unchanged. JAK inhibitor ruxolitinib ablated STAT1 and dACE2 expression after interferon treatment. Finally, with RNA-seq, we identified a set of genes, largely immune-related, induced by cytokine treatment. These gene expression profiles provide new insights into cytokine response of proximal tubule cells.

scholarly journals Inhibition of Osteoblast Proliferation and Migration by Exogenous and Endogenous Formaldehyde

2019 ◽  
Author(s):  
Xu Teng ◽  
Wei Huang ◽  
Hefeng Yu ◽  
Pei Wang ◽  
Weishi Li ◽  
...  
Keyword(s):  
Cell Growth ◽  
Potential Role ◽  
Expression Patterns ◽  
Cell Counting ◽  
Rna Seq ◽  
Cell Growth And Migration ◽  
Naturally Occurring ◽  
Significant Enrichment ◽  
And Migration ◽  
Proliferation And Migration

AbstractExogenous and endogenous formaldehyde (FA) plays an important role in cell growth and migration; however, its potential role in osteoblasts remains largely unclear. Cell counting kit-8 (CCK-8) and wound healing assays revealed that FA exposure at naturally occurring concentrations inhibited the proliferation and migration of mouse preosteoblast MC3T3-E1 cells. Moreover, RNA sequencing (RNA-seq) analysis revealed that FoxO1 signaling pathway components displayed distinct expression patterns upon FA exposure, reflected through significant enrichment of cell migration. In particular, FoxO1 Sirt1 and FA-induced related protein expression which were closely with cell proliferation and migration were confirmed by western blotting. The present results indicate that the FoxO1 pathway is involved in FA-induced inhibition of cell growth and migration.

scholarly journals Defining the function of SUMO system in pod development and abiotic stresses in Peanut

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yiyang Liu ◽  
Jiao Zhu ◽  
Sheng Sun ◽  
Feng Cui ◽  
Yan Han ◽  
...  
Keyword(s):  
Abiotic Stresses ◽  
Developmental Process ◽  
Expression Patterns ◽  
Rna Seq ◽  
Specific Expression ◽  
Genome Wide ◽  
Pod Development ◽  
Core Components ◽  
Arachis Duranensis ◽  
New Strategies

Abstract Background Posttranslational modification of proteins by small ubiquitin like modifier (SUMO) proteins play an important role during the developmental process and in response to abiotic stresses in plants. However, little is known about SUMOylation in peanut (Arachis hypogaea L.), one of the world’s major food legume crops. In this study, we characterized the SUMOylation system from the diploid progenitor genomes of peanut, Arachis duranensis (AA) and Arachis ipaensis (BB). Results Genome-wide analysis revealed the presence of 40 SUMO system genes in A. duranensis and A. ipaensis. Our results showed that peanut also encodes a novel class II isotype of the SCE1, which was previously reported to be uniquely present in cereals. RNA-seq data showed that the core components of the SUMOylation cascade SUMO1/2 and SCE1 genes exhibited pod-specific expression patterns, implying coordinated regulation during pod development. Furthermore, both transcripts and conjugate profiles revealed that SUMOylation has significant roles during the pod development. Moreover, dynamic changes in the SUMO conjugates were observed in response to abiotic stresses. Conclusions The identification and organization of peanut SUMO system revealed SUMOylation has important roles during stress defense and pod development. The present study will serve as a resource for providing new strategies to enhance agronomic yield and reveal the mechanism of peanut pod development.

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