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An integrative multi-omic analysis reveals a major metabolic rewiring between keratinocytes from babies and adults.

ABSTRACT: An integrative multi-omic analysis reveals a major metabolic rewiring between keratinocytes from babies and adults.

PROVIDER: PRJNA762291 | ENA |

REPOSITORIES: ENA

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An integrative multi-omic analysis reveals a major metabolic rewiring between keratinocytes from babies and adults.

Project description:Even though its development starts early in utero, neonatal skin is still immature at birth relative to adult and undergoes a maturation process extending to the first years of life. It is now established that stratum corneum is thinner and dryer, and that skin contains less natural moisturizing factors and lipids in newborns compared to children and adults. Moreover, it has been shown that skin surface area expansion is not linear throughout life and is peaking perinatally, suggesting that baby skin has a higher epidermal cellular turnover. Despite growing resources showing differences between adult and infant skin physiology, molecular and metabolic specificities of baby skin are still poorly understood. To address this critical knowledge gap, we performed an integrative transcriptomic and metabolomic study comparing human primary keratinocytes from babies and adults. Based on state-of-the-art integrative frameworks, our analyses revealed a major shift in the global energetic metabolism in baby keratinocytes compared to adults, highlighting increased amino acid metabolism and mitochondrial oxidative phosphorylation in baby cells to fuel TCA cycle, while showing glycolysis as the major cell energy source in adult cells.

2021-09-12 | GSE183891 | GEO

An integrative multi-omic analysis reveals a major metabolic rewiring between baby foreskin keratinocytes and adult female abdominal keratinocytes.

Project description:Even though its development starts early in utero, neonatal skin is still immature at birth relative to adult and undergoes a maturation process extending to the first years of life. It is now established that the stratum corneum is thinner and dryer and that skin contains less natural moisturizing factors and lipids in newborns compared to children and adults. Moreover, it has been shown that skin surface area expansion is not linear throughout life and is peaking perinatally, suggesting that baby skin has a higher epidermal cellular turnover. Despite growing resources showing differences between adult and infant skin physiology, molecular and metabolic specificities of baby skin are still poorly understood. To address this critical knowledge gap, we performed an integrative transcriptomic and metabolomic study comparing human primary foreskin and abdominal keratinocytes from male babies and female adults, respectively. Based on state-of-the-art integrative frameworks, our analyses revealed a major shift in the global energetic metabolism in baby foreskin keratinocytes compared to adult abdominal keratinocytes, highlighting increased amino acid metabolism and mitochondrial oxidative phosphorylation in baby cells to fuel the citric acid cycle, while showing glycolysis as the major cell energy source in adult cells.

| S-EPMC9299729 | biostudies-literature

Dissecting the molecular rewiring facilited by Pp6 deletion in keratinocytes

Project description:RNA-seq of keratinocytes derived from Pp6fl/fl and K5.Pp6fl/fl mice

2018-11-20 | GSE122665 | GEO

Temporal multi-omic profiling reveals chemoradiotherapy-specific dualistic metabolic rewiring that supports glioblastoma tumor recurrence

Project description:Temporal multi-omic profiling reveals chemoradiotherapy-specific dualistic metabolic rewiring that supports glioblastoma tumor recurrence

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multi-omic analysis

Project description:multi-omic analysis

| PRJNA790956 | ENA

Temporal multi-omic profiling reveals chemoradiotherapy-specific dualistic metabolic rewiring that supports glioblastoma tumor recurrence (Bulk RNA-Seq)

Project description:Temporal multi-omic profiling reveals chemoradiotherapy-specific dualistic metabolic rewiring that supports glioblastoma tumor recurrence (Bulk RNA-Seq)

| PRJNA1065856 | ENA

A transcriptomic analysis of primary fibroblasts isolated from young donors identifies a subset of donors displaying features of early senescence

2021-10-12 | GSE185679 | GEO

Cytokine stimulated keratinocytes

Project description:Cytokine stimulated keratinocytes

| PRJNA1076598 | ENA

Expression data from autophagy-deficient keratinocytes and normal keratinocytes

Project description:Expression data from autophagy-deficient keratinocytes and normal keratinocytes

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Hsa-miR-31-5p controls a metabolic switch in psoriatic keratinocytes that identifies therapeutic intervention

Project description:Next to genetic alterations, it is being recognized that the cellular environment also acts as a major determinant in onset and progression of disease. In cases where different cell types contribute to the final disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. A number of skin diseases, including psoriasis is characterized by a combination of keratinocyte hyperproliferation and immune cell activation. Activation of immune cells involves increased glucose consumption thereby intrinsicly limiting glucose availability for other cell types. Thus, these type of skin diseases require metabolic adaptations that enable coexistence between hyperproliferative keratinocytes and activated immune cells in a nutrient-limited environment. Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes within the psoriatic skin. Here we show that miR-31 expression in keratinocytes is induced by limited glucose availability and enables increased survival of keratinocytes under limiting glucose conditions, by increasing glutamine metabolism. In addition, miR-31 induced glutamine metabolism results in secretion of specific metabolites (aspartate and glutamate) but also secretion of immuno-modulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibition of glutaminase (GLS) using CB-839 impedes miR31-induced metabolic rewiring and secretion of immuno-modulatory factors. Concordantly, pharmacological targeting of GLS alleviated psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis.

2023-02-06 | PXD029030 | Pride

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