Transcriptomic Signature Differences Between SARS-CoV-2 and Influenza Virus Infected Patients

The reason why most individuals with COVID-19 have relatively limited symptoms while other develop respiratory distress with life-threatening complications remains unknown. Increasing evidence suggests that COVID-19 associated adverse outcomes mainly rely on dysregulated immunity. Here, we compared transcriptomic profiles of blood cells from 103 patients with different severity levels of COVID-19 with that of 27 healthy and 22 influenza-infected individuals. Data provided a complete overview of SARS-CoV-2-induced immune signature, including a dramatic defect in IFN responses, a reduction of toxicity-related molecules in NK cells, an increased degranulation of neutrophils, a dysregulation of T cells, a dramatic increase in B cell function and immunoglobulin production, as well as an important over-expression of genes involved in metabolism and cell cycle in patients infected with SARS-CoV-2 compared to those infected with influenza viruses. These features also differed according to COVID-19 severity. Overall and specific gene expression patterns across groups can be visualized on an interactive website (https://bix.unil.ch/covid/). Collectively, these transcriptomic host responses to SARS-CoV-2 infection are discussed in the context of current studies, thereby improving our understanding of COVID-19 pathogenesis and shaping the severity level of COVID-19.

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Differential gene expression in Drosophila melanogaster and D. nigrosparsa infected with the same Wolbachia strain

10.1101/2020.02.19.941534 ◽

2020 ◽

Author(s):

Matsapume Detcharoen ◽

Martin P. Schilling ◽

Wolfgang Arthofer ◽

Birgit C. Schlick-Steiner ◽

Florian M. Steiner

Keyword(s):

Gene Expression ◽

Drosophila Melanogaster ◽

Differential Gene Expression ◽

Expression Patterns ◽

Specific Gene ◽

Positive Effects ◽

Arthropod Species ◽

Expression Of Genes ◽

Novel Host ◽

Differential Gene

AbstractWolbachia, maternally inherited endosymbionts, infect nearly half of all arthropod species. Wolbachia manipulate their hosts to maximize their transmission, but they can also provide benefits such as nutrients and resistance to viruses for their hosts. The Wolbachia strain wMel was recently found to increase locomotor activities and possibly trigger cytoplasmic incompatibility in the fly Drosophila nigrosparsa. Here, we compared differential gene expression in Drosophila melanogaster (original host) and D. nigrosparsa (novel host), both uninfected and infected with wMel, using RNA sequencing to see if the two Drosophila species respond to the infection in the same or different ways. A total of 2164 orthologous genes were used. We found species-specific gene expression patterns. Significant changes shared by the fly species were confined to the expression of genes involved in heme binding and oxidation-reduction; the two host species differently changed the expression of genes when infected. Some of the genes were down-regulated in the infected D. nigrosparsa, which might indicate small positive effects of Wolbachia. We discuss our findings also in the light of how Wolbachia survive within both the native and the novel host.

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NtbHLH1, a JAF13-like bHLH, interacts with NtMYB6 to enhance proanthocyanidin accumulation in Chinese Narcissus

BMC Plant Biology ◽

10.1186/s12870-021-03050-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuxin Fan ◽

Jiayu Peng ◽

Jiacheng Wu ◽

Ping Zhou ◽

Ruijie He ◽

...

Keyword(s):

Flavonoid Biosynthesis ◽

Transcriptional Level ◽

Flavonoid Pathway ◽

Regulation Of Expression ◽

Over Expression ◽

Expression Of Genes ◽

Genes Encoding ◽

Regulatory Complex ◽

Positive Regulators ◽

R2r3 Myb

Abstract Background Flavonoid biosynthesis in plants is primarily regulated at the transcriptional level by transcription factors modulating the expression of genes encoding enzymes in the flavonoid pathway. One of the most studied transcription factor complexes involved in this regulation consists of a MYB, bHLH and WD40. However, in Chinese Narcissus (Narcissus tazetta L. var. chinensis), a popular monocot bulb flower, the regulatory mechanism of flavonoid biosynthesis remains unclear. Results In this work, genes related to the regulatory complex, NtbHLH1 and a R2R3-MYB NtMYB6, were cloned from Chinese Narcissus. Phylogenetic analysis indicated that NtbHLH1 belongs to the JAF13 clade of bHLH IIIf subgroup, while NtMYB6 was highly homologous to positive regulators of proanthocyanidin biosynthesis. Both NtbHLH1 and NtMYB6 have highest expression levels in basal plates of Narcissus, where there is an accumulation of proanthocyanidin. Ectopic over expression of NtbHLH1 in tobacco resulted in an increase in anthocyanin accumulation in flowers, and an up-regulation of expression of the endogenous tobacco bHLH AN1 and flavonoid biosynthesis genes. In contrast, the expression level of LAR gene was significantly increased in NtMYB6-transgenic tobacco. Dual luciferase assays showed that co-infiltration of NtbHLH1 and NtMYB6 significantly activated the promoter of Chinese Narcissus DFR gene. Furthermore, a yeast two-hybrid assay confirmed that NtbHLH1 interacts with NtMYB6. Conclusions Our results suggest that NtbHLH1 may function as a regulatory partner by interacting directly with NtMYB6 to enhance proanthocyanidin accumulation in Chinese Narcissus.

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Longitudinal Expression of Testicular TAS1R3 from Prepuberty to Sexual Maturity in Congjiang Xiang Pigs

Animals ◽

10.3390/ani11020437 ◽

2021 ◽

Vol 11 (2) ◽

pp. 437

Author(s):

Ting Gong ◽

Weiyong Wang ◽

Houqiang Xu ◽

Yi Yang ◽

Xiang Chen ◽

...

Keyword(s):

Sexual Maturity ◽

Cell Function ◽

Expression Patterns ◽

Taste Receptor ◽

Receptor Type ◽

Mrna Levels ◽

Early Puberty ◽

Specific Expression

Testicular expression of taste receptor type 1 subunit 3 (T1R3), a sweet/umami taste receptor, has been implicated in spermatogenesis and steroidogenesis in mice. We explored the role of testicular T1R3 in porcine postnatal development using the Congjiang Xiang pig, a rare Chinese miniature pig breed. Based on testicular weights, morphology, and testosterone levels, four key developmental stages were identified in the pig at postnatal days 15–180 (prepuberty: 30 day; early puberty: 60 day; late puberty: 90 day; sexual maturity: 120 day). During development, testicular T1R3 exhibited stage-dependent and cell-specific expression patterns. In particular, T1R3 levels increased significantly from prepuberty to puberty (p < 0.05), and expression remained high until sexual maturity (p < 0.05), similar to results for phospholipase Cβ2 (PLCβ2). The strong expressions of T1R3/PLCβ2 were observed at the cytoplasm of elongating/elongated spermatids and Leydig cells. In the eight-stage cycle of the seminiferous epithelium in pigs, T1R3/PLCβ2 levels were higher in the spermatogenic epithelium at stages II–VI than at the other stages, and the strong expressions were detected in elongating/elongated spermatids and residual bodies. The message RNA (mRNA) levels of taste receptor type 1 subunit 1 (T1R1) in the testis showed a similar trend to levels of T1R3. These data indicate a possible role of T1R3 in the regulation of spermatid differentiation and Leydig cell function.

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The Coordinated Upregulated Expression of Genes Involved in MEP, Chlorophyll, Carotenoid and Tocopherol Pathways, Mirrored the Corresponding Metabolite Contents in Rice Leaves during De-Etiolation

Plants ◽

10.3390/plants10071456 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1456

Author(s):

Xin Jin ◽

Can Baysal ◽

Margit Drapal ◽

Yanmin Sheng ◽

Xin Huang ◽

...

Keyword(s):

Higher Plants ◽

Expression Patterns ◽

Regulatory Elements ◽

Isoprenoid Biosynthesis ◽

Promoter Regions ◽

Expression Of Genes ◽

Coordinated Expression ◽

Rice Leaves ◽

Mechanistic Basis ◽

Phosphate Synthase

Light is an essential regulator of many developmental processes in higher plants. We investigated the effect of 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 1/2 genes (OsHDR1/2) and isopentenyl diphosphate isomerase 1/2 genes (OsIPPI1/2) on the biosynthesis of chlorophylls, carotenoids, and phytosterols in 14-day-old etiolated rice (Oyza sativa L.) leaves during de-etiolation. However, little is known about the effect of isoprenoid biosynthesis genes on the corresponding metabolites during the de-etiolation of etiolated rice leaves. The results showed that the levels of α-tocopherol were significantly increased in de-etiolated rice leaves. Similar to 1-deoxy-D-xylulose-5-phosphate synthase 3 gene (OsDXS3), both OsDXS1 and OsDXS2 genes encode functional 1-deoxy-D-xylulose-5-phosphate synthase (DXS) activities. Their expression patterns and the synthesis of chlorophyll, carotenoid, and tocopherol metabolites suggested that OsDXS1 is responsible for the biosynthesis of plastidial isoprenoids in de-etiolated rice leaves. The expression analysis of isoprenoid biosynthesis genes revealed that the coordinated expression of the MEP (2-C-methyl-D-erythritol 4-phosphate) pathway, chlorophyll, carotenoid, and tocopherol pathway genes mirrored the changes in the levels of the corresponding metabolites during de-etiolation. The underpinning mechanistic basis of coordinated light-upregulated gene expression was elucidated during the de-etiolation process, specifically the role of light-responsive cis-regulatory motifs in the promoter region of these genes. In silico promoter analysis showed that the light-responsive cis-regulatory elements presented in all the promoter regions of each light-upregulated gene, providing an important link between observed phenotype during de-etiolation and the molecular machinery controlling expression of these genes.

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A Global Vista of the Epigenomic State of the Mouse Submandibular Gland

Journal of Dental Research ◽

10.1177/00220345211012000 ◽

2021 ◽

pp. 002203452110120

Author(s):

C. Gluck ◽

S. Min ◽

A. Oyelakin ◽

M. Che ◽

E. Horeth ◽

...

Keyword(s):

Gene Expression ◽

Transcriptional Control ◽

Expression Patterns ◽

Global Gene Expression ◽

Regulatory Elements ◽

Specific Gene ◽

Submandibular Salivary Gland ◽

Data Sets ◽

Control Mechanisms ◽

Chromatin Immunoprecipitation Sequencing

The parotid, submandibular, and sublingual glands represent a trio of oral secretory glands whose primary function is to produce saliva, facilitate digestion of food, provide protection against microbes, and maintain oral health. While recent studies have begun to shed light on the global gene expression patterns and profiles of salivary glands, particularly those of mice, relatively little is known about the location and identity of transcriptional control elements. Here we have established the epigenomic landscape of the mouse submandibular salivary gland (SMG) by performing chromatin immunoprecipitation sequencing experiments for 4 key histone marks. Our analysis of the comprehensive SMG data sets and comparisons with those from other adult organs have identified critical enhancers and super-enhancers of the mouse SMG. By further integrating these findings with complementary RNA-sequencing based gene expression data, we have unearthed a number of molecular regulators such as members of the Fox family of transcription factors that are enriched and likely to be functionally relevant for SMG biology. Overall, our studies provide a powerful atlas of cis-regulatory elements that can be leveraged for better understanding the transcriptional control mechanisms of the mouse SMG, discovery of novel genetic switches, and modulating tissue-specific gene expression in a targeted fashion.

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

BMC Plant Biology ◽

10.1186/s12870-021-02879-w ◽

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.

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High HSPA8 expression predicts adverse outcomes of acute myeloid leukemia

BMC Cancer ◽

10.1186/s12885-021-08193-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jun Li ◽

Zheng Ge

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Prognostic Factor ◽

Myeloid Leukemia ◽

Cell Function ◽

Adverse Outcomes ◽

High Expression ◽

Micro Rnas ◽

Acute Myeloid

Abstract Background Acute myeloid leukemia (AML) remains one of the most common hematological malignancies, posing a serious challenge to human health. HSPA8 is a chaperone protein that facilitates proper protein folding. It contributes to various activities of cell function and also is associated with various types of cancers. To date, the role of HSPA8 in AML is still undetermined. Methods In this study, public datasets available from the TCGA (Cancer Genome Atlas) and GEO (Gene Expression Omnibus) were mined to discover the association between the expression of HSPA8 and clinical phenotypes of CN-AML. A series of bioinformatics analysis methods, including functional annotation and miRNA-mRNA regulation network analysis, were employed to investigate the role of HSPA8 in CN-AML. Results HSPA8 was highly expressed in the AML patients compared to the healthy controls. The high HSPA8 expression had lower overall survival (OS) rate than those with low HSPA8 expression. High expression of HSPA8 was also an independent prognostic factor for overall survival (OS) of CN-AML patients by multivariate analysis. The differential expressed genes (DEGs) associated with HSPA8 high expression were identified, and they were enriched PI3k-Akt signaling, cAMP signaling, calcium signaling pathway. HSPA8 high expression was also positively associated with micro-RNAs (hsa-mir-1269a, hsa-mir-508-3p, hsa-mir-203a), the micro-RNAs targeted genes (VSTM4, RHOB, HOBX7) and key known oncogenes (KLF5, RAN, and IDH1), and negatively associated with tumor suppressors (KLF12, PRKG1, TRPS1, NOTCH1, RORA). Conclusions Our research revealed HSPA8 as a novel potential prognostic factor to predict the survival of CN-AML patients. Our data also revealed the possible carcinogenic mechanism and the complicated microRNA-mRNA network associated with the HSPA8 high expression in AML.

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Set1 Targets Genes with Essential Identity and Tumor-Suppressing Functions in Planarian Stem Cells

Genes ◽

10.3390/genes12081182 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1182

Author(s):

Prince Verma ◽

Court K. M. Waterbury ◽

Elizabeth M. Duncan

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Mammalian Cells ◽

Cell Function ◽

Genotoxic Stress ◽

Specific Gene ◽

Cell Identity ◽

Chromatin Signature ◽

Lysine Methyltransferase

Tumor suppressor genes (TSGs) are essential for normal cellular function in multicellular organisms, but many TSGs and tumor-suppressing mechanisms remain unknown. Planarian flatworms exhibit particularly robust tumor suppression, yet the specific mechanisms underlying this trait remain unclear. Here, we analyze histone H3 lysine 4 trimethylation (H3K4me3) signal across the planarian genome to determine if the broad H3K4me3 chromatin signature that marks essential cell identity genes and TSGs in mammalian cells is conserved in this valuable model of in vivo stem cell function. We find that this signature is indeed conserved on the planarian genome and that the lysine methyltransferase Set1 is largely responsible for creating it at both cell identity and putative TSG loci. In addition, we show that depletion of set1 in planarians induces stem cell phenotypes that suggest loss of TSG function, including hyperproliferation and an abnormal DNA damage response (DDR). Importantly, this work establishes that Set1 targets specific gene loci in planarian stem cells and marks them with a conserved chromatin signature. Moreover, our data strongly suggest that Set1 activity at these genes has important functional consequences both during normal homeostasis and in response to genotoxic stress.

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Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons

Scientific Reports ◽

10.1038/s41598-021-84667-y ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Rebecca Rani Das Gupta ◽

Louis Scheurer ◽

Pawel Pelczar ◽

Hendrik Wildner ◽

Hanns Ulrich Zeilhofer

Keyword(s):

Spinal Cord ◽

Dorsal Horn ◽

Functional Organization ◽

Affinity Purification ◽

Expression Patterns ◽

Inhibitory Neurons ◽

Dorsal Horn Neurons ◽

Expression Of Genes ◽

Excitatory Neurons ◽

Genes Encoding

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (vGluT2+) and inhibitory GABA and/or glycinergic (vGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are not only set apart, as expected, by the expression of genes related to the production, release or re-uptake of their principal neurotransmitters and by genes encoding for transcription factors, but also by a differential engagement of neuromodulator, especially neuropeptide, signaling pathways. Subsequent multiplex in situ hybridization revealed eleven neuropeptide genes that are strongly enriched in excitatory dorsal horn neurons and display largely non-overlapping expression patterns closely adhering to the laminar and presumably also functional organization of the spinal cord grey matter.

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Comprehensive analysis of single cell ATAC-seq data with SnapATAC

Nature Communications ◽

10.1038/s41467-021-21583-9 ◽

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.

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