FGF7 and FGF10 Promote Fate Transition of Human Epidermal Cell-derived Organoids to an Eccrine Gland Phenotype

Epidermal appendages play a key role in thermoregulation, which is crucial in maintaining the equilibrium of body temperature. The normality of eccrine sweat glands (SwGs) and hair follicles (HFs) assures homeostatic thermoregulation. However, the fate commitments of SwGs and HFs development and their key regulators are still poorly understood. To elucidate the regulatory networks and the major regulators in SwGs and HFs development, we generated a transcriptomic atlas within three tissues (dorsal back skin, front and hinder ventral foot skin) across four early development stages (embryonic (E) days E15.5 and E17.5, postnatal (P) days P1 and P3) of Mus musculus. We then applied a second-order polynomial model to fit time-course expression of genes and used likelihood ratio test (LRT) to identify temporal dynamic expressed genes. We further constructed temporal regulatory networks to investigate the master regulators during different developmental stages. We found the distinct temporally developmental patterns between dorsal back and ventral foot skin. Eight temporally dynamic expression modes were inferred, which are comprised of over 90% of the dynamic genes. Shh, Eda, Bmp2 and other previously identified factors were noted in our dominant dynamic patterns as well and temporally dynamic expressed in dorsal back and ventral foot. Combined with differentially expressed genes analysis, we highlighted 501 genes that were common in front and hinder foot, albeit uniquely enrich or depleted in dorsal back. Moreover, the integration of temporal expression models and genes regulatory networks accentuated master transcription factors functioning at specific stages in different tissues. Our findings demonstrated the temporally dynamic determinants during SwGs and HFs fate commitments and can contribute to restoring impaired SwGs and HFs clinically after hypohidrosis or burn injury.