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

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. Human primary keratinocytes were provided by Sterlab (Sophia Antipolis, France) from 6 baby and 6 adult volunteers. Briefly, keratinocytes were isolated from foreskin and from abdominoplasty, for babies and adults respectively. Then, Keratinocytes were cultured in KGM gold basal medium supplemented with KGM-Gold Keratinocyte SingleQuots Kit (Lonza). One passage after thawing, RNAs were extracted using RNeasy 96 QIAcube HT Kit (Qiagen) and supernatants were collected. Samples were finally sent to Genex (Longjumeau, France) for transcriptomic analysis and Metabolon (Morrisville, USA) for metabolomic profiling.