Newborn infant skin gene expression: Remarkable differences versus adults
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ABSTRACT:
PROVIDER: PRJNA750434 | ENA |
REPOSITORIES: ENA
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Project description:At birth, human infants are poised to survive in harsh, hostile conditions. An understanding of the state of newborn skin development and maturation is key to the maintenance of health, optimum response to injury, healing and disease. The observational study collected full-thickness newborn skin samples from 27 infants at surgery and compared them to skin samples from 43 adult sites protected from ultraviolet radiation exposure, as the standard for stable, mature skin. Transcriptomics profiling and gene set enrichment analysis were performed. Statistical analysis established over 25,000 differentially regulated probe sets, representing 10,647 distinct genes, in infant skin compared to adult skin. Gene set enrichment analysis showed a significant increase in 143 biological processes (adjusted p < 0.01) in infant skin, versus adult skin samples, including extracellular matrix (ECM) organization, cell adhesion, collagen fibril organization and fatty acid metabolic process. The top two biological processes were ECM organization and ECM structure organization. Genes involving epidermis development, immune function, cell differentiation, and hair cycle were overexpressed in adults, representing 101 significantly enriched biological processes (adjusted p < 0.01). The top processes involved skin and epidermal development, e.g., keratinocyte differentiation, keratinization and cornification intermediate filament cytoskeleton organization and hair cycle. Over half of the enriched biological processes also involved immune function, including antigen processing and presentation. The results provide essential insight regarding newborn infant skin and its ability to support the newborn’s preparedness to survive and flourish, despite the infant’s new environment laden with microbes, high oxygen tension and potential irritants. To our knowledge, this is the first report on newborn infant skin transcriptomics analysis. When compared to ultraviolet radiation protected adult skin, it highlights the substantial differences between them. This fundamental knowledge is expected to guide strategies to protect and preserve the features of unperturbed, young skin.
2021-10-06 | GSE181022 | GEO
Project description:At birth, human infants are poised to survive in harsh, hostile conditions. An understanding of the state of newborn skin development and maturation is key to the maintenance of health, optimum response to injury, healing and disease. The observational study collected full-thickness newborn skin samples from 27 infants at surgery and compared them to skin samples from 43 adult sites protected from ultraviolet radiation exposure, as the standard for stable, mature skin. Transcriptomics profiling and gene set enrichment analysis were performed. Statistical analysis established over 25,000 differentially regulated probe sets, representing 10,647 distinct genes, in infant skin compared to adult skin. Gene set enrichment analysis showed a significant increase in 143 biological processes (adjusted p < 0.01) in infant skin, versus adult skin samples, including extracellular matrix (ECM) organization, cell adhesion, collagen fibril organization and fatty acid metabolic process. ECM organization and ECM structure organization were the biological processes in infant skin with the lowest adjusted P-value. Genes involving epidermal development, immune function, cell differentiation, and hair cycle were overexpressed in adults, representing 101 significantly enriched biological processes (adjusted p < 0.01). The processes with the highest significant difference were skin and epidermal development, e.g., keratinocyte differentiation, keratinization and cornification intermediate filament cytoskeleton organization and hair cycle. Enriched Gene Ontology (GO) biological processes also involved immune function, including antigen processing and presentation. When compared to ultraviolet radiation-protected adult skin, our results provide essential insight into infant skin and its ability to support the newborn's preparedness to survive and flourish, despite the infant's new environment laden with microbes, high oxygen tension and potential irritants. This fundamental knowledge is expected to guide strategies to protect and preserve the features of unperturbed, young skin.
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Project description:Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared to adults, although underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRM) mediate optimal protection to respiratory pathogens. We hypothesized that reduced protection in infancy was due to impaired T effector localization and/or lung TRM establishment. Using an infant mouse model we demonstrate generation of lung-homing, virus-specific T effectors following influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRM and heterosubtypic protection was reduced compared to adults. Impaired TRM establishment was infant-T cell-intrinsic and infant effectors displayed distinct transcriptional profiles enriched for T-bet-regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression following activation and reducing T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage.
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2019-12-27 | GSE131241 | GEO
Project description:The human thymus shows a transient involution along the neonatal period and starts a continuous process of decline between the 1st and 2nd years. The immune alterations associated to thymic aging in humans have been extensively investigated, but the genomic mechanisms underlying this process remain largely unknown. Here we conducted a temporal gene co-expression network analysis in the newborn and infant thymic tissue aiming to identify transcriptional modules associated to age.
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2023-08-16 | GSE237817 | GEO
Project description:The aggressive MLL-rearranged leukemias are well-known for their unique gene-expression profiles. The goal of this study was to characterize the MLL-specific DNA methylation profiles in infant acute lymphoblastic leukemia (ALL). Genome-wide DNA methylation profiling was performed on primary infant ALL samples. The majority of infant ALL samples demonstrated severe DNA hypermethylation compared with normal pediatric bone marrows, which implies that targeting of DNA methylation may be an interesting option for future therapeutic strategies in MLL-rearranged infant ALL. Using ALL cell lines carrying the MLL translocation t(4;11) (SEMK2 and RS4;11) as a model for the patient cells, we demonstrated that the hypermethylated genes are sensitive to demethylation.
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