Prenatal screening for miRNAs in fetal diseases
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE242364 | GEO | 2024/03/20
REPOSITORIES: GEO
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Project description:Congenital diaphragmatic hernia (CDH) is a severe birth defect frequently associated with pulmonary hypoplasia, pulmonary hypertension, and heart failure. Since amniotic fluid comprises proteins of both fetal and maternal origin, its analysis could provide insights on mechanisms underlying CDH and provide biomarkers for early diagnosis, severity of pulmonary changes and response to treatment. The study objective was to identify proteomic changes in amniotic fluid consistently associated with CDH. Amniotic fluid was obtained at term (37-39 weeks) from women with normal pregnancies (n=5) or carrying fetuses with CDH (n=5). After immuno-depletion of the highest abundance proteins, off-line fractionation and high-resolution tandem mass spectrometry were performed and quantitative differences between the proteomes of the groups were determined. Of 1036 proteins identified, 218 were differentially abundant. Bioinformatics analysis showed significant changes in GP6 signaling, MSP-RON signaling in macrophages pathways and networks associated with cardiovascular system development and function, connective tissue disorders and dermatological conditions. Pulmonary surfactant protein B, osteopontin, kallikrein 5 and galectin 3 were investigated orthogonally using ELISA in larger cohorts to test the observed differences and showed statistically significant differences aiding in the prediction of CDH. The findings provide potential tools for improved clinical detection and management of CDH.
2023-11-03 | PXD041859 | Pride
Project description:Congenital diaphragmatic hernia (CDH) results from incomplete diaphragm development and can be associated with pulmonary hypoplasia, pulmonary hypertension, and heart failure. Currently, few biomarkers are available. Since amniotic fluid comprises proteins of both fetal and maternal origin, its analysis could provide insights on mechanisms underlying CDH and provide biomarkers for early diagnosis, severity of pulmonary changes and response to treatment. The study objective was to identify proteomic changes in amniotic fluid consistently associated with CDH. Amniotic fluid was obtained at term (37-39 weeks) from women with normal pregnancies (n=5) or carrying fetuses with CDH (n=5). After immuno-depletion of the highest abundance proteins, off-line fractionation and high-resolution tandem mass spectrometry were performed and quantitative differences between the proteomes of the groups were determined. Of 1036 proteins identified, 218 were differentially abundant. Bioinformatics analysis showed significant changes in GP6 signaling, MSP-RON signaling in macrophages pathways and networks associated with cardiovascular system development and function, connective tissue disorders and dermatological conditions. Pulmonary surfactant protein B, osteopontin, kallikrein 5 and galectin 3 were investigated orthogonally using ELISA in larger cohorts to test the observed differences and showed statistically significant differences aiding in the prediction of CDH. The findings provide potential tools for improved clinical detection and management of CDH.
2023-10-24 | PXD041165 | Pride
Project description:Isolation of tissue-specific fetal stem cells and derivation of primary organoids is currently limited to post-termination samples. This hampers the prenatal investigation of fetal development and congenital diseases. Therefore, novel patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue or cellular reprogramming, would be advantageous. The amniotic fluid (AF) is a source of cells originating from multiple developing organs. Using single cell analysis, we characterised the cellular identities present in the human AF. We identified and isolated viable epithelial stem/progenitor cells of fetal gastrointestinal, renal and pulmonary origin. Upon culture, these cells formed clonal epithelial organoids, manifesting small intestine, kidney tubule and lung identity. AF organoids (AFO) exhibit transcriptomic, protein expression and functional features of their tissue of origin. With relevance for prenatal disease modelling, we derived lung organoids from the amniotic and tracheal fluid cells of Congenital Diaphragmatic Hernia (CDH) fetuses. CDH organoids show differences to non-CDH controls recapitulating some features of the disease. AFO are derived in a timeline compatible with prenatal intervention, potentially allowing investigation of therapeutic tools and regenerative medicine strategies personalised to the fetus at clinically relevant developmental stages.
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Project description:The production of skeletal muscle constructs useful for in vivo large defects replacement, such as congenital diaphragmatic hernia (CDH), is still considered a challenge. The standard application of prosthetic material presents strong limitations, like hernia recurrences in a remarkable number of CDH patients. With this work, we developed a tissue engineering approach based on decellularized diaphragmatic muscle and human cells for the generation in vitro of diaphragmatic-like tissues as proof-of-concept of a new option for the surgical treatment of large diaphragm defects. A specific bioreactor for diaphragmatic muscle was achieved to control mechanical stimulation during the construct generation. In vitro tests demonstrated the increased maturation of mechanically stimulated constructs, with the formation of new oriented and aligned muscle fibres. Moreover, after in vivo orthotopic implantation in a CDH mouse model, mechanically stimulated muscles maintained the presence of human cells within myofibers, supporting the idea of a new therapeutic option for this dramatic congenital malformation. Production of diaphragmatic-like tissues using mouse decellularized extracellular matrix, human cells and mechanical stimulation with bioreactor
2022-02-28 | GSE180636 | GEO
Project description:Microarray data from this study represent the first global transcriptional survey of gene expression during early compared to late diaphragm formation. Based on the assumption that Congenital diaphragmatic hernia (CDH) candidate genes will have similar temporal expression trends and will be part of the same biological pathways as those already implicated in CDH, we used known CDH-associated genes as “baits” to filter expression microarray data sets (GSEA and STEM) to identify a list of novel CDH candidate genes.
2012-02-10 | GSE35243 | GEO
Project description:Investigation into the effects of Congenital Diaphragmatic Hernia (CDH) and subsequent treatment with tracheal occlusion (TO) on the pulmonary transcriptome. A diaphragm defect was created by surgical means in fetal rabbits. The surgical creation of diaphragmatic hernia (DH) allows for direct analysis of changes in pulmonary gene expression due to pulmonary hypoplasia, without the need for gene knockdown (as for KO mice) or use of teratogens (such as nitrofen). The subsequent treatment with tracheal occlusion (TO) was also investigated to determine the changes in gene expression due to forced lung growth in the prenatal phase. RNA-Seq analysis was performed on left lung samples from fetal rabbits. Samples were generated and analysed for DH (n=4), TO (n=6), and control lungs (n=4)
2015-04-15 | E-MTAB-3452 | biostudies-arrayexpress
Project description:Microarray data from this study represent the first global transcriptional survey of gene expression during early compared to late diaphragm formation. Based on the assumption that Congenital diaphragmatic hernia (CDH) candidate genes will have similar temporal expression trends and will be part of the same biological pathways as those already implicated in CDH, we used known CDH-associated genes as “baits” to filter expression microarray data sets (GSEA and STEM) to identify a list of novel CDH candidate genes. Laser-capture microdissected C57BL/6J mouse embryonic diaphragm tissues were studied at three key time-points during normal development. We studied the primordial diaphragm’s pleuroperitoneal folds at E11.5 and E12.5, and the muscularized mature diaphragm at E16.5 to identify genes and pathways that characterize important stages in diaphragm morphogenesis.
2012-02-10 | E-GEOD-35243 | biostudies-arrayexpress
Project description:Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm and lung hypoplasia. The pathophysiology of lung defects in CDH is poorly understood. To establish a translational model of human airway epithelium in CDH for pathogenic investigation and therapeutic testing, we developed a robust methodology of epithelial progenitor derivation from tracheal aspirates of newborns. Basal stem cells from CDH patients and preterm and term, non-CDH controls were derived and analyzed by bulk RNA-sequencing, ATAC-sequencing, and air-liquid-interface differentiation. Transcriptomic and epigenetic profiling of CDH and non-CDH basal stem cells reveals a disease-specific, proinflammatory signature independent of severity or hernia size. In addition, CDH basal stem cells exhibit defective epithelial differentiation in vitro that recapitulates epithelial phenotypes found in fetal human CDH lung samples and fetal tracheas of the nitrofen rat model of CDH. Furthermore, steroid treatment normalizes epithelial differentiation phenotypes of human CDH basal stem cells in vitro and in nitrofen rat tracheas in vivo. Our findings have identified an interplay between a proinflammatory signature and BSC differentiation as a potential therapeutic target for airway epithelial defects in CDH.
2023-06-30 | GSE211789 | GEO
Project description:Congenital diaphragmatic hernia (CDH) is characterized by incomplete closure of the diaphragm and lung hypoplasia. The pathophysiology of lung defects in CDH is poorly understood. To establish a translational model of human airway epithelium in CDH for pathogenic investigation and therapeutic testing, we developed a robust methodology of epithelial progenitor derivation from tracheal aspirates of newborns. Basal stem cells from CDH patients and preterm and term, non-CDH controls were derived and analyzed by bulk RNA-sequencing, ATAC-sequencing, and air-liquid-interface differentiation. Transcriptomic and epigenetic profiling of CDH and non-CDH basal stem cells reveals a disease-specific, proinflammatory signature independent of severity or hernia size. In addition, CDH basal stem cells exhibit defective epithelial differentiation in vitro that recapitulates epithelial phenotypes found in fetal human CDH lung samples and fetal tracheas of the nitrofen rat model of CDH. Furthermore, steroid treatment normalizes epithelial differentiation phenotypes of human CDH basal stem cells in vitro and in nitrofen rat tracheas in vivo. Our findings have identified an interplay between a proinflammatory signature and BSC differentiation as a potential therapeutic target for airway epithelial defects in CDH.
2023-06-30 | GSE211788 | GEO
Project description:Gene Mutation and Rescue in Human Congenital Diaphragmatic Hernia (CDH)
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