Research Scientist POLA Chemical Industries, Inc. Singapore, Singapore
Abstract: Skin serves as a protective barrier against the harshness of the external environment. Advances in stem cell and organoid technologies have enabled the generation of hair-bearing skin organoids and an unprecedented way to probe human skin biology in vitro. However, the long lead time required to make them hampers their ease of application to a wide range of medical research. Here, we aim to reduce the time frame to generate skin organoids. We tested growth factors that are known to influence skin development and identified FGF10 that could reduce the time required for hair placodes to emerge from skin organoids by up to 14 days. Despite FGF10 treatment taking place only transiently in early organoid formation, its effect persisted till later timepoints and resulted in skin organoids developing mature hair follicles earlier than untreated counterparts. Importantly, FGF10 treatment did not cause any defects in mature skin organoids and their cellular composition. Mechanistically, single-cell RNA sequencing analysis revealed a specific intermediate keratinocyte cluster that appeared just before hair placode formation in untreated organoids and which occurred only one week after FGF10 treatment, suggesting that its formation may be a key driver of accelerated skin organoid maturation. Collectively, the present study improved the protocol of skin organoid without any notable abnormality, boosting the potential of skin organoids for future investigation of human skin development and their use as therapeutic grafts.
