Global Transcriptomic Profiling of Pulmonary Gene Expression in an Experimental Murine Model of Rickettsia conorii Infection
Abstract
:1. Introduction
2. Material and Methods
2.1. Mammalian Cell Culture and Preparation of Rickettsia conorii Stocks
2.2. Mouse Model of Infection
2.3. Purification of Total RNA, Complementary DNA Library Preparation, and RNA Sequencing
2.4. Mapping of Deep Sequencing Data and Ingenuity Pathway Analysis
2.5. Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR)
2.6. Statistical Analysis
3. Results
3.1. Transcriptome Sequencing, Assembly, and Analysis of Mouse Lungs During In Vivo R. conorii Infection
3.2. Validation of RNA-Sequencing Data by Quantitative Real-Time PCR
3.3. Functional Annotation and Classification of Transcriptome Data
3.4. Signatures of Inflammation and Tissue Damage
3.5. Antimicrobial Peptides
3.6. Activation or Inhibition of Upstream Signaling Regulators
3.7. Canonical Pathways
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Symbol | Gene Name | p-Value | FDR (q-Value) | FC | Log2 FC |
---|---|---|---|---|---|
Up-regulated molecules | |||||
Ubd | Ubiquitin D | 0 | 0 | 679.8 | 9.4 |
Acod1 | Aconitate decarboxylase 1 | 0 | 0 | 433.9 | 8.8 |
Cxcl9 | Chemokine (C-X-C motif) ligand 9 | 0 | 0 | 405.4 | 8.7 |
Ido1 | Indoleamine 2,3-dioxygenase 1 | 0 | 0 | 332.3 | 8.4 |
Cxcl10 | C-X-C motif chemokine ligand 10 | 0 | 0 | 331.6 | 8.4 |
Ly6a | Lymphocyte antigen 6 complex, locus A | 0 | 0 | 223.2 | 7.8 |
Camp | Cathelicidin antimicrobial peptide | 0 | 0 | 204 | 7.7 |
Ngp | Neutrophilic granule protein | 0 | 0 | 168 | 7.4 |
Gzmk | Granzyme K | 0 | 0 | 135.7 | 7.1 |
Gbp6 | Guanylate binding protein family member 6 | 0 | 0 | 127.8 | 7 |
Ifn-γ | Interferon γ | 0 | 0 | 119.8 | 6.9 |
Serpina3g | Serine (or cysteine) peptidase inhibitor, clade A, member 3G | 0 | 0 | 117.5 | 6.9 |
Gzmb | Granzyme B | 0 | 0 | 103.9 | 6.7 |
Gzma | Granzyme A | 0 | 0 | 90.4 | 6.5 |
Klrg1 | Killer cell lectin like receptor G1 | 0 | 0 | 87.7 | 6.5 |
Ccl7 | Chemokine (C-C motif) ligand 7 | 0 | 0 | 83.9 | 6.4 |
Ccl2 | Chemokine (C-C motif) ligand 2 | 0 | 0 | 74.8 | 6.2 |
Tgtp1/Tgtp2 | T cell specific GTPase 1 | 0 | 0 | 73.4 | 6.2 |
Gbp5 | Guanylate binding protein 5 | 0 | 0 | 59.1 | 5.9 |
Xcl1 | X-C motif chemokine ligand 1 | 0 | 0 | 52.6 | 5.7 |
Calhm6 | Calcium homeostasis modulator family member 6 | 0 | 0 | 52.2 | 5.7 |
Down-regulated molecules | |||||
Hbb-bt | Hemoglobin subunit β | 0 | 0 | −25.2 | −4.7 |
Hba1/Hba2 | Hemoglobin subunit α 2 | 0 | 0 | −22 | −4.5 |
Alas2 | 5’-aminolevulinate synthase 2 | 0 | 0 | −13.3 | −3.7 |
Cyp26b1 | Cytochrome P450 family 26 subfamily B member 1 | 3 × 10−7 | 0.000005 | −10.2 | −3.3 |
Alb | Albumin | 0.000546 | 0.00461 | −9.2 | −3.2 |
Hey1 | Hes related family bHLH transcription factor with YRPW motif 1 | 0 | 0 | −6.9 | −2.8 |
Aplnr | Apelin receptor | 0 | 0 | −6.6 | −2.7 |
Nr1d1 | Nuclear receptor subfamily 1 group D member 1 | 0 | 0 | −5.9 | −2.6 |
Ptprb | Protein tyrosine phosphatase, receptor type B | 0 | 0 | −5.8 | −2.5 |
Dll4 | Delta like canonical Notch ligand 4 | 0 | 0 | −5.7 | −2.5 |
Efnb2 | Ephrin B2 | 0 | 0 | −5.1 | −2.3 |
Ltbp4 | Latent transforming growth factor β binding protein 4 | 0 | 0 | −5 | −2.3 |
Hmcn1 | Hemicentin 1 | 0 | 0 | −4.9 | −2.3 |
Angptl2 | Angiopoietin like 2 | 0 | 0 | −4.7 | −2.2 |
Ednrb | Endothelin receptor type B | 0 | 0 | −4.1 | −2 |
Spock2 | SPARC/osteonectin, cwcv and kazal like domains proteoglycan 2 | 0 | 0 | −4.1 | −2 |
Sh3pxd2a | SH3 and PX domains 2A | 0 | 0 | −3.7 | −1.9 |
Ndst1 | N-deacetylase and N-sulfotransferase 1 | 0 | 0 | −3.7 | −1.9 |
Igfbp5 | Insulin like growth factor binding protein 5 | 6.68 × 10−7 | 1.04 × 10−5 | −3.5 | −1.8 |
Pdgfrb | Platelet derived growth factor receptor β | 0 | 0 | −3.5 | −1.8 |
Regulator | Molecule Type | p-Value | Activation z-Score |
---|---|---|---|
Activated upstream regulators | |||
Irf3 | Transcription regulator | 2.21 × 10−24 | 6.8 |
Ifn-γ | Cytokine | 1.82 × 10−27 | 6.5 |
Ticam1 | Other | 4.13 × 10−22 | 6.3 |
Irf7 | Transcription regulator | 1.62 × 10−24 | 5.8 |
Stat1 | Transcription regulator | 1.62 × 10−17 | 5.7 |
Myd88 | Other | 8.02 × 10−20 | 5.5 |
Cd38 | Enzyme | 1.17 × 10−8 | 5.5 |
Samsn1 | Other | 5.86 × 10−12 | 5.4 |
Il5 | Cytokine | 3.07 × 10−9 | 5.2 |
Rb1 | Transcription regulator | 8.56 × 10−6 | 4.9 |
Dock8 | Other | 5.24 × 10−11 | 4.9 |
Sash1 | Other | 1.03 × 10−9 | 4.8 |
Tlr4 | Transmembrane receptor | 4.04 × 10−16 | 4.7 |
Nfatc2 | Transcription regulator | 1.88 × 10−8 | 4.6 |
Tnf | Cytokine | 3.54 × 10−13 | 4.6 |
Chuk | Kinase | 9.36 × 10−14 | 4.5 |
Mavs | Other | 1.04 × 10−14 | 4.3 |
Arhgap21 | Other | 7.33 × 10−7 | 4.1 |
Ikbkb | Kinase | 8.43 × 10−17 | 4.1 |
Irf5 | Transcription regulator | 2.48 × 10−9 | 4 |
Inhibited upstream regulators | |||
Il10ra | Transmembrane receptor | 1.85 × 10−19 | −7.4 |
Ptger4 | G-protein coupled receptor | 9.94 × 10−16 | −6 |
Kdm5a | Transcription regulator | 4.61 × 10−7 | −5.2 |
Socs1 | Other | 1.19 × 10−15 | −4.6 |
Irgm1 | Other | 2.56 × 10−10 | −4 |
Bcl6 | Transcription regulator | 7.76 × 10−5 | −3.6 |
Srf | Transcription regulator | 0.000721 | −3.4 |
Nr3c1 | Ligand-dependent nuclear receptor | 7.27 × 10−8 | −3.4 |
Gfi1 | Transcription regulator | 0.000536 | −3.3 |
Ncstn | Peptidase | 2.48 × 10−9 | −3.3 |
Apoe | Transporter | 5.75 × 10−6 | −2.9 |
Por | Enzyme | 5.08 × 10−5 | −2.9 |
Dusp1 | Phosphatase | 0.013 | −2.7 |
C5 | Cytokine | 0.0151 | −2.6 |
Tgfbr1 | Kinase | 0.0333 | −2.6 |
Dicer1 | Enzyme | 0.00974 | −2.6 |
Stat6 | Transcription regulator | 5.24 × 10−14 | −2.5 |
Cyb5r4 | Enzyme | 0.000106 | −2.4 |
Abcg1 | Transporter | 0.00048 | −2.4 |
Irf9 | Transcription regulator | 2.32 × 10−8 | −2.3 |
Canonical Pathway Name | p-Value | Differentially Expressed Genes/Total Number of Genes in the Pathway |
---|---|---|
EIF2 Signaling | 1.54 × 10−42 | 100/205 (48.8%) |
Oxidative Phosphorylation | 1.29 × 10−21 | 48/96 (50.0%) |
Mitochondrial Dysfunction | 3.29 × 10−19 | 59/153 (38.6%) |
Antigen Presentation Pathway | 3.90 × 10−18 | 23/28 (82.1%) |
Protein Ubiquitination Pathway | 1.33 × 10−15 | 72/245 (29.4%) |
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Narra, H.P.; Sahni, A.; Khanipov, K.; Fofanov, Y.; Sahni, S.K. Global Transcriptomic Profiling of Pulmonary Gene Expression in an Experimental Murine Model of Rickettsia conorii Infection. Genes 2019, 10, 204. https://doi.org/10.3390/genes10030204
Narra HP, Sahni A, Khanipov K, Fofanov Y, Sahni SK. Global Transcriptomic Profiling of Pulmonary Gene Expression in an Experimental Murine Model of Rickettsia conorii Infection. Genes. 2019; 10(3):204. https://doi.org/10.3390/genes10030204
Chicago/Turabian StyleNarra, Hema P., Abha Sahni, Kamil Khanipov, Yuriy Fofanov, and Sanjeev K. Sahni. 2019. "Global Transcriptomic Profiling of Pulmonary Gene Expression in an Experimental Murine Model of Rickettsia conorii Infection" Genes 10, no. 3: 204. https://doi.org/10.3390/genes10030204
APA StyleNarra, H. P., Sahni, A., Khanipov, K., Fofanov, Y., & Sahni, S. K. (2019). Global Transcriptomic Profiling of Pulmonary Gene Expression in an Experimental Murine Model of Rickettsia conorii Infection. Genes, 10(3), 204. https://doi.org/10.3390/genes10030204