DNA methylation signatures in airway cells from adult children of asthmatic mothers reflect subtypes of severe asthma
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PROVIDER: PRJNA867702 | ENA |
REPOSITORIES: ENA
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Project description:Maternal asthma (MA) is among the most consistent risk factors for asthma in her children. Possible mechanisms for this observation are epigenetic modifications in utero that have lasting effects on developmental programs in children of mothers with asthma. To test this hypothesis, we performed differential DNA methylation analyses of 398,186 individual CpG sites in primary bronchial epithelial cells (BECs) from 42 non-asthma controls and 88 asthma cases, including 56 without MA (NMA) and 32 with MA. We used weighted gene co-expression network analysis (WGCNA) of 69 and 554 differentially methylated CpGs (DMCs) that were specific to NMA or MA cases, respectively, compared to controls. WGCNA grouped 66 NMA-DMCs and 203 MA-DMCs into two and five co-methylation modules, respectively. The eigenvector of one MA-associated module (turquoise) was uniquely correlated with 85 genes expressed in BECs and enriched for 36 pathways, 16 of which discriminated between NMA and MA using machine learning. Genes in all 16 pathways were decreased in MA compared to NMA cases (P=7.1x10-3), a finding that replicated in nasal epithelial cells from an independent cohort (P=0.02). Functional interpretation of these pathways suggested impaired T cell signaling and responses to viral and bacterial pathogens. The MA-associated turquoise module eigenvector was additionally correlated with clinical features of severe asthma and reflective of type 2 (T2)-low asthma (i.e., low total serum IgE, fractional exhaled nitric oxide, and eosinophilia). Overall, these data suggest that maternal asthma alters diverse epigenetically-mediated pathways that lead to distinct subtypes of severe asthma in adults including hard-to-treat T2-low asthma.
2022-05-02 | GSE201872 | GEO
Project description:Maternal asthma (MA) is among the most consistent risk factors for asthma in her children. Possible mechanisms for this observation are epigenetic modifications in utero that have lasting effects on developmental programs in children of mothers with asthma. To test this hypothesis, we performed differential DNA methylation analyses of 398,186 individual CpG sites in primary bronchial epithelial cells (BECs) from 42 non-asthma controls and 88 asthma cases, including 56 without MA (NMA) and 32 with MA. We used weighted gene co-expression network analysis (WGCNA) of 69 and 554 differentially methylated CpGs (DMCs) that were specific to NMA or MA cases, respectively, compared to controls. WGCNA grouped 66 NMA-DMCs and 203 MA-DMCs into two and five co-methylation modules, respectively. The eigenvector of one MA-associated module (turquoise) was uniquely correlated with 85 genes expressed in BECs and enriched for 36 pathways, 16 of which discriminated between NMA and MA using machine learning. Genes in all 16 pathways were decreased in MA compared to NMA cases (P=7.1x10-3), a finding that replicated in nasal epithelial cells from an independent cohort (P=0.02). Functional interpretation of these pathways suggested impaired T cell signaling and responses to viral and bacterial pathogens. The MA-associated turquoise module eigenvector was additionally correlated with clinical features of severe asthma and reflective of type 2 (T2)-low asthma (i.e., low total serum IgE, fractional exhaled nitric oxide, and eosinophilia). Overall, these data suggest that maternal asthma alters diverse epigenetically-mediated pathways that lead to distinct subtypes of severe asthma in adults including hard-to-treat T2-low asthma.
2022-05-04 | GSE201955 | GEO
Project description:DNA methylation signatures in airway cells from adult children of asthmatic mothers reflect subtypes of severe asthma (RNA sequencing)
| PRJNA833856 | ENA
Project description:DNA methylation signatures in airway cells from adult children of asthmatic mothers reflect subtypes of severe asthma (DNA methylation)
| PRJNA833397 | ENA
Project description:Background The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception. Objective To assess whether the trajectory to asthma begins already at birth and epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception. Methods We used a combination of methyl binding protein-dependent DNA capture and microarrays to survey DNA methylation in cord blood mononuclear cells (CBMC) from 36 children (18 non-asthmatic, 18 asthmatic by age 9) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n=60) and in two replication cohorts (The Manchester Asthma and Allergy Study, n=30, and the Childhood Origins of ASThma Study, n=28) was analyzed by bisulfite sequencing or Illumina 450K arrays. CBMC-derived IL-1b was measured by ELISA. Results Neonatal immune cells harbored 589 differentially methylated regions (DMRs) that distinguished IIS children who did and did not develop asthma by age 9. In all three cohorts, methylation in SMAD3, the most connected hub within the network of asthma-associated DMRs, was selectively increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk. Moreover, SMAD3 methylation in IIS neonates with maternal asthma was strongly and positively associated with neonatal production of IL-1b, an innate inflammatory mediator. Conclusions The trajectory to childhood asthma begins at birth and involves epigenetic modifications in immunoregulatory and pro-inflammatory pathways. Maternal asthma influences epigenetic mechanisms that contribute to the inception of this trajectory.
2017-04-13 | GSE85228 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-08-09 | GSE210843 | GEO
Project description:This study aims to demonstrate the link between epigenome-wide methylation aberrations at birth and genomic transcriptional changes upon allergen sensitization that occur in the neonatal dendritic cells (DC) due to maternal asthma. In an in vivo model reproducing human epidemiology findings, maternal but not paternal asthma predisposes the neonate to increased asthma risk, the effect is allergen-independent and is not genetic or environmental. Earlier we demonstrated that neonates of asthmatic mothers are born with a functional skew in splenic DCs that mediates the early-life asthma origin. These allergen-naive cells convey allergy responses to normal recipients, however minimal to no transcriptional or phenotypic changes were found to explain the functional pro-allergic alterations. In this study we profiled both allergen-naïve dendritic cells, and cells after allergen sensitization in vivo. We found that while allergen-naive DCs from asthma-at-risk neonates have minimal transcriptional change compared to controls, upon allergen sensitization, multiple genes with pre-existing epigenetic alterations show significant transcriptional change. . 24 samples from 2 batches, 3-4 replicates in each of 4 groups
2013-06-01 | E-GEOD-44678 | biostudies-arrayexpress
Project description:This study aims to demonstrate the link between epigenome-wide methylation aberrations at birth and genomic transcriptional changes upon allergen sensitization that occur in the neonatal dendritic cells (DC) due to maternal asthma. In an in vivo model reproducing human epidemiology findings, maternal but not paternal asthma predisposes the neonate to increased asthma risk, the effect is allergen-independent and is not genetic or environmental. Earlier we demonstrated that neonates of asthmatic mothers are born with a functional skew in splenic DCs that mediates the early-life asthma origin. These allergen-naive cells convey allergy responses to normal recipients, however minimal to no transcriptional or phenotypic changes were found to explain the functional pro-allergic alterations. In this study we profiled both allergen-naïve dendritic cells, and cells after allergen sensitization in vivo. We found that while allergen-naive DCs from asthma-at-risk neonates have minimal transcriptional change compared to controls, upon allergen sensitization, multiple genes with pre-existing epigenetic alterations show significant transcriptional change. .
2013-06-01 | GSE44678 | GEO
Project description:Asthma is a very frequent airway disease that affects 6 to 20% of the population. Severe asthma, represents 3 to 5% of all asthmatic patients and is histologically characterized by an increased bronchial smooth muscle (BSM) mass and clinically by viral exacerbations. Functionally, BSM remodeling had a poor prognostic value in asthma, since higher BSM mass was associated with lower lung function and increased exacerbation rate. However, the role of BSM as a potential actor of asthma exacerbation has only been sparsely suggested. Thus, we hypothesis that asthmatic BSM cell metabolism is modified compare to that of non-asthmatic and that could be a potential target to reduce asthmatic BSM cell proliferation and remodeling in asthma.
2021-06-10 | PXD015566 | Pride
Project description:Asthma is a very frequent airway disease that affects 6 to 20% of the population. Severe asthma, represents 3 to 5% of all asthmatic patients and is histologically characterized by an increased bronchial smooth muscle (BSM) mass and clinically by viral exacerbations. Functionally, BSM remodeling had a poor prognostic value in asthma, since higher BSM mass was associated with lower lung function and increased exacerbation rate. However, the role of BSM as a potential actor of asthma exacerbation has only been sparsely suggested. We thus hypothesis that asthmatic BSM cells could act on bronchial epithelium and modified its response to rhinovirus infection.
2023-05-02 | PXD015604 | Pride