Edem Tchegnon

Dry eye disease affects over 16 million adults in the US, and the majority of cases are due to Meibomian gland dysfunction. Unfortunately, the identity of the stem cells involved in Meibomian gland development and homeostasis is not well elucidated. Here, we report that loss of Krox20 , a zinc finger transcription factor involved in the development of ectoderm-derived tissues, or deletion of KROX20-expressing epithelial cells disrupted Meibomian gland formation and homeostasis, leading to dry eye disease secondary to Meibomian gland dysfunction. Ablation of Krox20 -lineage cells in adult mice also resulted in dry eye disease, implicating Krox20 in homeostasis of the mature Meibomian gland. Lineage-tracing and expression analyses revealed a restricted KROX20 expression pattern in the ductal areas of the Meibomian gland, although Krox20 -lineage cells generate the full, mature Meibomian gland. This suggests that KROX20 marks a stem/progenitor cell population that differentiates to generate the entire Meibomian gland. Our Krox20 mouse models provide a powerful system that delineated the identity of stem cells required for Meibomian gland development and homeostasis and can be used to investigate the factors underlying these processes. They are also robust models of Meibomian gland dysfunction–related dry eye disease, with a potential for use in preclinical therapeutic screening.

Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell tumor neurofibroma is the most prevalent. A hallmark feature of neurofibroma is mast cell infiltration, which is recruited by chemoattractant stem cell factor (SCF) and has been suggested to sustain neurofibroma tumorigenesis. In the present study, we use new, genetically engineered Scf mice to decipher the contributions of tumor-derived SCF and mast cells to neurofibroma development. We demonstrate that mast cell infiltration is dependent on SCF from tumor Schwann cells. However, removal of mast cells by depleting the main SCF source only slightly affects neurofibroma progression. Other inflammation signatures show that all neurofibromas are associated with high levels of macrophages regardless of Scf status. These findings suggest an active inflammation in neurofibromas and partly explain why mast cell removal alone is not sufficient to relieve tumor burden in this experimental neurofibroma model. Furthermore, we show that plexiform neurofibromas are highly associated with injury-prone spinal nerves that are close to flexible vertebras. In summary, our study details the role of inflammation in neurofibromagenesis. Our data indicate that prevention of inflammation and possibly also nerve injury at the observed tumor locations are therapeutic approaches for neurofibroma prophylaxis and that such treatment should be explored.

A large portion of natural products research revolves around the discovery of new, bioactive chemical entities; however, studies to probe the biological purpose of such secondary metabolites for the host organism are often limited. Mass spectrometry mapping of secondary metabolite biosynthesis in situ can be used to probe a series of ecological questions about fungi that may be lost through traditional natural products chemistry extraction protocols. A griseofulvin-producing fungal culture of the Xylariaceae family, isolated as an endophyte of the tree Asimina triloba, was analyzed through a series of spatial and temporal mapping experiments. This fungus produced unique fungal characteristics, such as guttates and stroma, both of which were explored spatially. The distribution of griseofulvin on this culture in isolation was compared to its dispersal when grown in co-culture with a competing Penicillium species via a droplet–based surface sampling system. The fungistatic properties of griseofulvin were visualized, including the consequences for biosynthesis of polyhydroxyanthraquinones in a rival culture.