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Results for “comparative transcriptomics”

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PubMed2005

Analysis of the growth phase-associated transcriptome of Streptococcus pyogenes.

Streptococcus pyogenes (group A streptococci, GAS) is a human pathogen which probably varies its multiplication rate and thus, growth phases in association with the type of infection caused in its host. To create a basis for future determinations of such associations, the genome-wide growth phase-related GAS transcriptome was assessed in the present study. Therefore, the published serotype M1 S. pyogenes genome sequence as well as the partially sequenced serotype M18 and M49 GAS genomes were used to produce DNA microarrays that carried 2256 oligonucleotide probes matching 3662 open reading frames (ORFs). With these microarrays, the transcriptome of the serotype M49 GAS strain 591 grown to the exponential, transition, and early stationary growth phases was assessed in seven independent experiments. The gained data were compared to real-time RT-PCR assays. Data analysis was refined by a novel approach, i.e. grouping of expressed genes to four classes according to relative transcript abundance and gene functions. At the different growth phases, 86.7%, 79.5% and 55.7% of the at least 1883 ORFs contained in the serotype M49 genome were expressed above the defined detection level. Contrary to the general trend, transcript amounts of genes in the functional groups of transport and membrane proteins as well as stress response factors peaked at the transition phase. The most prominent changes in the transcript abundances were predominantly observed for sugar compound transport and turnover-related ORFs. The majority of known virulence genes had their maximum expression during the transition phase, consistent with the proposed associated change in virulence behavior of the bacteria. With these results, it will now be feasible to assess the in situ growth phase of a given GAS strain during any type of infection by measuring the expression of selected marker genes.

DNA, Bacterial↗

PubMed2006

Transcriptome analysis of cold acclimation in barley albina and xantha mutants.

Previously, we have shown that barley (Hordeum vulgare) plants carrying a mutation preventing chloroplast development are completely frost susceptible as well as impaired in the expression of several cold-regulated genes. Here we investigated the transcriptome of barley albina and xantha mutants and the corresponding wild type to assess the effect of the chloroplast on expression of cold-regulated genes. First, by comparing control wild type against cold-hardened wild-type plants 2,735 probe sets with statistically significant changes (P = 0.05; > or = 2-fold change) were identified. Expression of these wild-type cold-regulated genes was then analyzed in control and cold-hardened mutants. Only about 11% of the genes cold regulated in wild type were regulated to a similar extent in all genotypes (chloroplast-independent cold-regulated genes); this class includes many genes known to be under C-repeat binding factor control. C-repeat binding factor genes were also equally induced in mutants and wild-type plants. About 67% of wild-type cold-regulated genes were not regulated by cold in any mutant (chloroplast-dependent cold-regulated genes). We found that the lack of cold regulation in the mutants is due to the presence of signaling pathway(s) normally cold activated in wild type but constitutively active in the mutants, as well as to the disruption of low-temperature signaling pathway(s) due to the absence of active chloroplasts. We also found that photooxidative stress signaling pathway is constitutively active in the mutants. These results demonstrate the major role of the chloroplast in the control of the molecular adaptation to cold.

Acclimatization↗

PubMed2006

The transcriptome of the uterine cervix before and after spontaneous term parturition.

OBJECTIVE: This study was designed to identify genes differentially expressed in the human uterine cervix after spontaneous term labor. STUDY DESIGN: The transcriptome of cervical tissue was characterized using Affymetrix HG-U133 plus 2 microarrays. Samples were collected from patients at term not in labor (n = 7) and after spontaneous labor (n = 9). Microarray statistical analysis included robust multiarray average, reduction of invariant probes, and permutation analysis for differential expression. Real-time quantitative reverse transcriptase-polymerase chain reaction assays of selected genes were performed on a new set of samples from term patients without labor (n = 10) and patients after spontaneous labor (n = 9). RESULTS: (1) The cervical transcriptome of term patients without labor was dramatically different from that of patients who underwent labor; (2) unique genes (n = 1192) were differentially expressed in the cervical tissue from patients after spontaneous labor, compared with that of the term patients without labor (false discovery rate less than 0.05, absolute fold change greater than 2); (3) Gene Ontology analysis indicated that multiple "Biological Process" categories were enriched, including "response to biotic stimulus," "apoptosis," "epidermis development," and "steroid metabolism"; (4) of major interest, genes involved in neutrophil chemotaxis were dramatically up-regulated in specimens from women after spontaneous labor; (5) real-time quantitative reverse transcriptase-polymerase chain reaction confirmed the increased expression of interleukin-8, interleukin-6, and vascular endothelial growth factor in patients after spontaneous labor; and (6) Toll-like receptor-3 and Toll-like receptor-5 showed decreased gene expression in patients after spontaneous labor. This was confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction. CONCLUSION: (1) Cervical dilatation in term labor is associated with a stereotypic gene expression pattern determined by microarray, which is characterized by overexpression of genes involved in neutrophil chemotaxis, apoptosis, extracellular matrix regulation, and steroid metabolism; (2) Toll-like receptor-3 and Toll-like receptor-5 are differentially regulated during spontaneous parturition at term; and (3) this study provides an unbiased and comprehensive description of the changes in the cervical transcriptome before and after spontaneous term labor.

Adolescent↗

PubMed2002

Sepsis gene expression profiling: murine splenic compared with hepatic responses determined by using complementary DNA microarrays.

OBJECTIVE: DNA microarrays allow genome-wide assessment of changes in relative messenger RNA abundance and thus can be used to monitor changes in gene expression. The aim of this series of experiments was to gain experience in sepsis gene expression profiling in a well-accepted model of murine polymicrobial abdominal sepsis and begin characterizing (in the parlance of genomics) the sepsis "transcriptome." DESIGN: Prospective animal study. SETTING: University-based animal research facility.SUBJECTS C57BL/6 mice. INTERVENTIONS: After induction of general anesthesia, cecal ligation and puncture were performed to induce peritonitis and polymicrobial sepsis. The control group had sham laparotomy only. Three samples of spleen and liver were collected from septic and sham animals at 24 hrs after laparotomy. Changes in expression were measured for 588 annotated mouse genes by using a commercially available complementary DNA microarray kit. MEASUREMENTS AND MAIN RESULTS: Broad-scale gene expression profiles were characterized for septic liver and spleen and compared with sham controls. The analytical tools used included commercially available software packages and a novel analysis program. Very little overlap was observed in the septic gene expression profiles of these two organs. Most of the genes identified have previously been linked to regulation of the inflammatory response; importantly, however, some have not. In addition, hierarchical cluster analysis showed that cecal ligation and puncture at 24 hrs induced coordinate expression of genes that alter cell signaling and survival pathways in spleen, consistent with previously published reports of sepsis-induced splenocyte apoptosis. The current limitations of microarray analysis as reflected in these studies are also discussed. CONCLUSIONS: Microarray technology provides a powerful new tool for rapidly analyzing tissue-specific changes in gene expression induced by sepsis in animal models. To our knowledge, these data constitute the first report on the use of microarrays to determine the sepsis transcriptome.

Animals↗

PubMed2002

Transcriptome analysis documents induced competence of Bacillus subtilis during nitrogen limiting conditions.

DNA microarrays were used to analyze the changes in gene expression in Bacillus subtilis strain 168 when nitrogen limiting (glutamate) and nitrogen excess (ammonium plus glutamate) growth conditions were compared. Among more than 100 genes that were significantly induced during nitrogen starvation we detected the comG, comF, comE, nin-nucA and comK transcription units together with recA. DNA was added to B. subtilis grown in minimal medium with glutamate as the sole nitrogen source and it was demonstrated that the cells were competent. Based on these observations we propose a simplification of previously designed one-step transformation procedures for B. subtilis strain 168.

Bacillus subtilis↗

PubMed2026

A contextual activity score (CAS) for inferring ADAR-associated transcriptional activity across RNA-seq, single-cell, and spatial transcriptomics.

BACKGROUND AND OBJECTIVE: Adenosine-to-inosine RNA editing, catalyzed by Adenosine Deaminases Acting on RNA (ADARs), is a widespread modification involved in neural function, immune regulation, and cancer. The Alu Editing Index (AEI) is the standard metric to estimate ADAR activity but requires raw sequencing reads and is poorly suited for single-cell and spatial transcriptomic data. This study aimed to develop an alternative framework for inferring ADAR-associated transcriptional activity from gene expression data across diverse transcriptomic technologies. METHODS: We developed the Contextual Activity Score (CAS), a framework based on transcriptional signatures from ADAR perturbation experiments. Context-specific signatures were generated for human neurons, mouse neurons, and cancer models to infer ADAR1 and ADAR2 activity. CAS was computed from normalized gene expression matrices using regulon-based enrichment analysis. Performance was evaluated by comparing with the Alu Editing Index across bulk RNA sequencing datasets, simulated sequencing depths, and library preparation protocols. RESULTS: CAS showed strong concordance with the Alu Editing Index across multiple datasets, while remaining robust to reduced sequencing depth and different library protocols. Unlike the Alu Editing Index, CAS can be applied to single-cell and spatial transcriptomic data and enables the independent assessment of ADAR2 activity. In cancer and neuronal contexts, CAS captured biologically meaningful variations in ADAR-associated transcriptional activity at sample, cell-type, and spatial levels. CONCLUSION: CAS provides a scalable approach applicable across multiple RNA-seq protocols for estimating ADAR-associated transcriptional activity using gene expression data. This method, implemented in an open-source R package for broad adoption, expands the ability to study ADAR-associated transcriptional activity across transcriptomic modalities where direct editing quantification is challenging, such as single-cell and spatial transcriptomics.

Adenosine Deaminase↗

PubMed2003

Kinesin superfamily proteins (KIFs) in the mouse transcriptome.

In the post genomic era where virtually all the genes and the proteins are known, an important task is to provide a comprehensive analysis of the expression of important classes of genes, such as those that are required for intracellular transport. We report the comprehensive analysis of the Kinesin Superfamily, which is the first and only large protein family whose constituents have been completely identified and confirmed in silico and at the cDNA, mRNA level. In FANTOM2, we have found 90 clones from 33 Kinesin Superfamily Protein (KIF) gene loci. The clones were analyzed in reference to sequence state, library of origin, detection methods, and alternative splicing. More than half of the representative transcriptional units (TU) were full length. The FANTOM2 library also contains novel splice variants previously unreported. We have compared and evaluated various protein classification tools and protein search methods using this data set. This report provides a foundation for future research of the intracellular transport along microtubules and proves the significance of intracellular transport protein transcripts as part of the transcriptome.

Alternative Splicing↗

PubMed2006

Introduction of silencing-inducing transgenes does not affect expression of known transcripts.

While the RNA interference (RNAi) mechanism has only been discovered a decade ago, RNAi is now often used to study gene function by sequence-specific knockdown of gene expression. However, it is still unknown whether introduction of silencing-inducing transgenes alters the transcriptome. To address this question, genome-wide transcriptional changes in silenced and non-silenced backgrounds were monitored through microarray analysis. No significant transcriptional changes were detected when compared to the non-silenced control. This result was confirmed by real-time polymerase chain reaction analysis of genes known to be involved in RNA silencing. In conclusion, introduction of silencing-inducing constructs does not affect expression of known transcripts in other genes than in those homologous to the targeted ones. Consequently, when gene function is studied by RNAi, the transcriptional changes detected will specifically be the result of knockout of the gene of interest, at least for the genes present on the array used in our study.

Arabidopsis↗

PubMed2003

Monitoring expression profiles of rice genes under cold, drought, and high-salinity stresses and abscisic acid application using cDNA microarray and RNA gel-blot analyses.

To identify cold-, drought-, high-salinity-, and/or abscisic acid (ABA)-inducible genes in rice (Oryza sativa), we prepared a rice cDNA microarray including about 1700 independent cDNAs derived from cDNA libraries prepared from drought-, cold-, and high-salinity-treated rice plants. We confirmed stress-inducible expression of the candidate genes selected by microarray analysis using RNA gel-blot analysis and finally identified a total of 73 genes as stress inducible including 58 novel unreported genes in rice. Among them, 36, 62, 57, and 43 genes were induced by cold, drought, high salinity, and ABA, respectively. We observed a strong association in the expression of stress-responsive genes and found 15 genes that responded to all four treatments. Venn diagram analysis revealed greater cross talk between signaling pathways for drought, ABA, and high-salinity stresses than between signaling pathways for cold and ABA stresses or cold and high-salinity stresses in rice. The rice genome database search enabled us not only to identify possible known cis-acting elements in the promoter regions of several stress-inducible genes but also to expect the existence of novel cis-acting elements involved in stress-responsive gene expression in rice stress-inducible promoters. Comparative analysis of Arabidopsis and rice showed that among the 73 stress-inducible rice genes, 51 already have been reported in Arabidopsis with similar function or gene name. Transcriptome analysis revealed novel stress-inducible genes, suggesting some differences between Arabidopsis and rice in their response to stress.

Abscisic Acid↗

PubMed2006

Microarray analysis of the transcriptome as a stepping stone towards understanding biological systems: practical considerations and perspectives.

DNA microarrays have been used to characterize plant transcriptomes to answer various biological questions. While many studies have provided significant insights, there has been great debate about the general reliability of the technology and data analysis. When compared to well-established transcript analysis technologies, such as RNA blot analysis or quantitative reverse transcription-PCR, discrepancies have frequently been observed. The reasons for these discrepancies often relate to the technical and experimental systems. This review-tutorial addresses common problems in microarray analysis and describes: (i) methods to maximize extraction of valuable biological information from the vast amount of microarray data and (ii) approaches to balance resource availability with high scientific standards and technological innovation with peer acceptability.

Blotting, Northern↗

PubMed2006

High degree of conservancy among secreted salivary gland proteins from two geographically distant Phlebotomus duboscqi sandflies populations (Mali and Kenya).

BACKGROUND: Salivary proteins from sandflies are potential targets for exploitation as vaccines to control Leishmania infection; in this work we tested the hypothesis that salivary proteins from geographically distant Phlebotomus duboscqi sandfly populations are highly divergent due to the pressure exerted by the host immune response. Salivary gland cDNA libraries were prepared from wild-caught P. duboscqi from Mali and recently colonised flies of the same species from Kenya. RESULTS: Transcriptome and proteome analysis resulted in the identification of the most abundant salivary gland-secreted proteins. Orthologues of these salivary proteins were identified by phylogenetic tree analysis. Moreover, comparative analysis between the orthologues of these two different populations resulted in a high level of protein identity, including the predicted MHC class II T-cell epitopes from all these salivary proteins. CONCLUSION: These data refute the hypothesis that salivary proteins from geographically distinct populations of the same Phlebotomus sandfly species are highly divergent. They also suggest the potential for using the same species-specific components in a potential vector saliva-based vaccine.

Africa, Eastern↗

PubMed2006

Multiple sclerosis therapy monitoring based on gene expression.

Multiple sclerosis (MS) is the most prevalent chronic autoimmune, neurodegenerative disorder of the central nervous system (CNS). Despite substantial progress, treatment of MS and other autoimmune diseases is only moderately effective. It is anticipated that the treatment of autoimmune diseases with single drugs or biological approaches will in the future be complemented, or even replaced, by combination therapies, which include immunomodulation, elimination of infectious triggers and tissue repair. One proclaimed goal of biomedical research and clinical practice is the discovery of sets of genes with expression that correlates with successful outcomes of drug therapy, or with unfortunate side effects. Such information has direct consequences for selection, refinement or development of treatments and will soon be translated into clinical trials. The genome-wide RNA profile of an individual represents one complement to the comprehensive determination of disease- or drug response-related elements; comparable to a 'sentinel' method, it serves as a large-scale approach to MS biology. This work reviews the state of the art in MS research at the transcriptome level applying genomewide screening methods. It discusses implications in understanding disease pathogenicity, diagnostic markers, the identification of new therapeutic targets and a classification of patients towards the advent of tailored therapies.

Biomarkers↗

PubMed2026

Single-cell transcriptomics reveals that air-liquid interface culture promotes goblet cell differentiation and inhibits glycolysis in organoid cell monolayers.

Faithfully recapitulating the cellular heterogeneity of the intestinal epithelium is essential when using organoid models. Air-liquid interface (ALI) culture has been shown to promote secretory cell differentiation, but its impact on gene expression in each epithelial cell type remains unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to characterize the cellular heterogeneity of rabbit cecum-derived organoid monolayers grown under immerged or ALI conditions. We then compared these organoid cell type-specific gene expression profiles to a scRNA-seq atlas of the rabbit cecal epithelium in vivo. We selected the rabbit model notably because, unlike mice, it possesses BEST4+ epithelial cells, a newly discovered subset of mature absorptive cells. Our analysis revealed a high degree of transcriptomic similarity between in vivo and organoid-derived stem and transit-amplifying cells. ALI culture markedly enhanced the differentiation of the secretory lineage, especially goblet cells, whose transcriptome closely resembled that of in vivo goblet cells. Furthermore, ALI was the only condition allowing the detection of enteroendocrine cells. BEST4+ cells, however, were absent from organoids in immerged or ALI conditions despite their presence in vivo. In addition, ALI culture led to a consistent downregulation of hypoxia and glycolysis-associated genes across all cell types, which suggests a metabolic shift likely driven by increased oxygen availability in ALI conditions. Cell-cell communication analyses further indicated that ALI more closely mirrored in vivo patterns than immerged condition. Altogether, these results demonstrate that ALI culture allows for better recapitulation of the in vivo cellular heterogeneity and molecular signatures of the intestinal epithelium.NEW & NOTEWORTHY Using single-cell RNA sequencing, this study shows that air-liquid interface (ALI) culture enhances secretory lineage differentiation of intestinal organoid cell monolayers and improves transcriptomic similarity to the native epithelium. ALI reduced hypoxia-associated gene expression and better recapitulates in vivo-like cell-cell interactions, supporting its value for modeling intestinal epithelial heterogeneity in organoids.

Animals↗

PubMed2006

Gene expression profiles of different breast cancer cells compared with their responsiveness to fermented mistletoe (Viscum album L.) extracts Iscador from oak (Quercus), pine (Pinus), white fir (Abies) and apple tree (Malus) in vitro.

Cytotoxicity assays in vitro (MTT test) showed that the different breast cancer cell lines Kpl-1, MCF-7 and Mfm-223 respond differently to the mistletoe (Viscum album L.) preparations Iscador. Quercus (Qu), Abies (A), Malus (M) and Pinus (P). In order to determine the differences in the responsiveness of the cells more exactly, the gene expression profiles were determined by cells, which were treated with Mistletoe extracts, compared with untreated control cells. Such differences can be analysed in more detail by looking at the gene expression using Human Whole Genome microarray chips (41,000 genes). The results of the transcriptome analyses suggested that Iscador preparations influenced the overregulation of genes regarding immune defense, stress response, apoptosis and cell-cell adhesion pathways. Within the Mfm-223-Zellen was the Genexpression in MCF-7 and Kpl-1. The MCF-7 cells were affected on the genes which are involved in cell-cell contacts whereas Kpl-1 responded to the mistletoe extracts by changing the mRNA levels of the immune and stress response pathways. Concerning the effects of the mistletoe extract, we conclude that Iscador Qu and M have a greater influence on the immune defense and stress response genes whereas Iscador A tends to affect the cell-cell adhesion and cytoskeleton pathways. In summary, cDNA microarray analyses give us information on whether a cancer cell is sensitive to mistletoe extracts in relation to how many genes are significantly overrepresented after mistletoe treatment, and whether a particular mistletoe extract is more effective on a specific cancer cell than the other preparation.

Abies↗

PubMed2026

Evolutionary and resistance dynamics in oligometastatic and oligoprogressive cancer treated with stereotactic radiotherapy and systemic therapies: A systematic review and focused meta-analysis.

BACKGROUND: Oligometastatic and oligoprogressive disease treated with stereotactic ablative radiotherapy (SABR) represents a clinically heterogeneous entity. Increasing evidence suggests that anatomical definitions alone may not adequately capture underlying biological diversity. This systematic review aimed to synthesize translational evidence exploring evolutionary dynamics, resistance mechanisms, and biomarker-driven stratification in patients treated with SABR. METHODS: A systematic literature review was performed including prospective and retrospective studies evaluating translational biomarkers in oligometastatic or oligoprogressive settings treated with SABR. Studies assessing genomic, transcriptomic, circulating or immune-related biomarkers were included. Data were summarized qualitatively according to predefined translational domains: (i) evolutionary dynamics under systemic therapy pressure, (ii) baseline biological stratification, (iii) longitudinal circulating biomarkers, and (iv) systemic immune remodeling. Exploratory quantitative visual syntheses were performed using reported hazard ratios when conceptually comparable endpoints were available. RESULTS: 19 studies comprising 1527 patients were included. Across tumor types and treatment contexts, translational analyses consistently indicated that anatomically defined oligometastatic states encompass biologically distinct subgroups with different risks of systemic progression. Studies evaluating oligoprogression under ongoing systemic therapy suggested a distinction between spatially constrained resistance and systemic molecular escape, supported by circulating tumor DNA and tissue- or plasma-based molecular profiling (including genomic and transcriptomic analyses). Baseline biological features, including adverse genomic signatures and circulating biomarkers, were associated with inferior progression outcomes despite metastasis-directed therapy. Longitudinal biomarkers provided early signals of treatment response and systemic control. Immune remodeling after SABR showed context-dependent effects, both systemic immune activation and treatment-related immunosuppression reported across studies.

Humans↗

PubMed2004

Sequential extracellular matrix-focused and baited-global cluster analysis of serial transcriptomic profiles identifies candidate modulators of renal tubulointerstitial fibrosis in murine adriamycin-induced nephropathy.

Transcriptome analysis using microarray technology represents a powerful unbiased approach for delineating pathogenic mechanisms in disease. Here molecular mechanisms of renal tubulointerstitial fibrosis (TIF) were probed by monitoring changes in the renal transcriptome in a glomerular disease-dependent model of TIF (adriamycin nephropathy) using Affymetrix (mu74av2) microarray coupled with sequential primary biological function-focused and secondary "baited"-global cluster analysis of gene expression profiles. Primary cluster analysis focused on mRNAs encoding matrix proteins and modulators of matrix turnover as classified by Onto-Compare and Gene Ontology and identified both molecules and pathways already implicated in the pathogenesis of TIF (e.g. transforming growth factor beta1-CTGF-fibronectin-1 pathway) and novel TIF-associated genes (e.g. SPARC and Matrilin-2). Specific gene expression patterns identified by primary extracellular matrix-focused cluster analysis were then used as bioinformatic bait in secondary global clustering, with which to search the renal transcriptome for novel modulators of TIF. Among the genes clustering with ECM proteins in the latter analysis were endoglin, clusterin, and gelsolin. In several notable cases (e.g. claudin-1 and meprin-1beta) the pattern of gene expression identified in adriamycin nephropathy in vivo was replicated during transdifferentiation of renal tubule epithelial cells to a fibroblast-like phenotype in vitro on exposure to transforming growth factor-beta and epidermal growth factor suggesting a role in fibrogenesis. The further exploration of these complex gene networks should shed light on the core molecular pathways that underpin TIF in renal disease.

Animals↗

PubMed2026

A regulatory network underlying idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease in which genetic susceptibility interacts with epithelial, immune, and mesenchymal remodeling. Although the chromosome 11p15.5 locus contains established IPF susceptibility signals near MUC5B and TOLLIP, the broader regulatory architecture of this region remains incompletely resolved. METHODS: We integrated IPF genome-wide association study summary statistics with methylation, expression, and protein quantitative trait loci using summary-data-based Mendelian randomization (SMR). SMR-prioritized candidates were evaluated in independent transcriptomic and methylation cohorts and further contextualized using microRNA, transcription-factor, protein-interaction, machine-learning, single-cell, and spatial transcriptomic analyses. Fibrosis-associated expression patterns were assessed in a bleomycin-induced pulmonary fibrosis rat model. RESULTS: The analyses recovered the established MUC5B and TOLLIP signals and prioritized BRSK2 as a comparatively underexplored candidate supported by eQTL-based SMR and independent molecular evidence. The BRSK2 pQTL association did not pass the HEIDI test and was therefore not interpreted as convergent protein-level genetic evidence. Network analyses linked BRSK2 to cell-cycle, metabolic-stress, and senescence-related programs, while cross-cohort machine learning prioritized FOXA2, CDC25B, and NFE2 as informative network features. Single-cell and spatial analyses localized BRSK2 preferentially to fibroblast and myofibroblast compartments and to regions with greater histological fibrosis severity. In fibrotic rat lungs, BRSK2 expression increased, whereas FOXA2 and CDC25B decreased at the transcript and protein levels. CONCLUSIONS: These findings refine the molecular landscape of the chromosome 11p15.5 IPF susceptibility locus and prioritize BRSK2 as a candidate component of an IPF-associated profibrotic fibroblast state. Its causal contribution, direct regulatory relationships, and therapeutic tractability require targeted mechanistic validation.

Idiopathic Pulmonary Fibrosis↗

PubMed2006

Connexin43 and the brain transcriptome of newborn mice.

Our previously reported cDNA array datasets from neonatal wild-type and Cx43-/- (approved gene symbol Gja1) mouse brains were further analyzed to identify underlying interlinkages in the brain transcriptome. The analysis revealed that no gene cohort sharing either primary function or chromosomal location was significantly altered (up-and down-regulation were roughly balanced) in Cx43-/- brains, but each cohort exhibited significant perturbation of transcript abundance proportions and reduced expression variability and coordination. By comparing pairwise expression correlations of all genes with one another in wild-type brains, we found genes exhibiting remarkable similarity or opposition to the coordination profile (set of synergistically, antagonistically, and independently expressed partners) of Cx43, one of the most similar being pannexin1, a vertebrate homolog of invertebrate gap junction proteins. This study indicates striking redundancy of expression controls over functional pathways and suggests that certain genes may play roles similar to or opposite that of Cx43 in organizing the brain transcriptome.

Animals↗