Biology subjects

Iomini, C.

Publications and source records attributed to Iomini, C..

3 recordsLinked to original sources

bioRxiv2024

Identification of Meibomian gland stem cell populations and mechanisms of aging

Meibomian glands secrete lipid-rich meibum, which prevents tear evaporation. Aging-related Meibomian gland shrinkage may result in part from stem cell exhaustion and is associated with evaporative dry eye disease, a common condition lacking effective treatment. The identities and niche of Meibomian gland stem cells and the signals controlling their activity are poorly defined. Using snRNA-seq, in vivo lineage tracing, ex vivo live imaging, and genetic studies in mice, we identified markers for stem cell populations that maintain distinct regions of the gland and uncovered Hh signaling as a key regulator of stem cell proliferation. Consistent with this, human Meibomian gland carcinoma exhibited increased Hh signaling. Aged glands displayed decreased Hh and EGF signaling, deficient innervation, and loss of collagen I in niche fibroblasts, indicating that alterations in both glandular epithelial cells and their surrounding microenvironment contribute to age-related degeneration. These findings suggest new approaches to treat aging-associated Meibomian gland loss.

cell biology↗

bioRxiv2022

Primary cilia regulate Meibomian glands development and dimensions without impairing the lipid composition of the meibum

PurposePrimary cilia regulate the development of various ectoderm-derived tissues, including the corneal epithelium, skin, hair follicle and sebaceous glands. We aimed to investigate their role in meibomian gland (MG) development. MethodsPrimary cilium ablation in MGs was achieved by crossing a floxed Ift88 mouse (Ift88fl/fl) with a mouse expressing the Cre recombinase under the keratin 14 (K14) promoter, to generate K14-Cre;Ift88fl/fl mice. MG morphology was evaluated by histology and immunostaining, as well as lipid staining and 2-photon microscopy on whole mount tarsal plates. MG lipid profiles were assessed by chromatography. ResultsWe showed that most of MG cells are ciliated during early stages of MG development and that MG ciliated rate decreases throughout morphogenesis. In morphologically mature glands, only the MG central duct and ductules are ciliated, and meibocytes lose their cilia as they differentiate and become filled with lipids. Primary cilium ablation induces enlargement of MGs, dilation of the MG central duct, and an increased production of lipids, without dramatically changing the lipid profiles. In addition, primary cilia regulate MG elongation and the spatial distribution of proliferating and dying cells within MGs, without changing the total cell proliferation and death rates. ConclusionsThese findings indicate that primary cilia are not necessary for normal MG development. However, they promote MG enlargement and lipid production, suggesting that primary cilia could be an interesting target for treatments of ocular surface diseases involving MGs, like dry eye disease.

developmental biology↗

bioRxiv2019

Primary cilia deficiency in neural crest cells causes Anterior Segment Dysgenesis

During eye embryogenesis, neural crest cells (NCC) of the periocular mesenchyme (POM) migrate to the anterior segment (AS) of the eye and then differentiate into the corneal stroma and endothelium, ciliary body, iris stroma, and the trabecular meshwork. Defective development of these structures leads to anterior segment dysgenesis (ASD) that in 50% of the cases leads to glaucoma, a leading cause of blindness. Here, we show that the primary cilium is indispensable for normal AS development and that its ablation in NCC induces ASD phenotypes including; small and thin cornea, impaired stromal keratocyte organization, abnormal iridocorneal angle with reduced anterior chamber and corneal neovascularization. These defects are similar to those described in patients with AS conditions such as Axenfeld-Rieger syndrome and Peters anomaly. Mechanistically, disruption of the primary cilium in the NCC resulted in reduced hedgehog (Hh) signaling in the POM, canonically activated by the Indian Hedgehog ligand expressed by endothelial cells of the choroid. This caused decreased cell proliferation in a subpopulation of POM cells surrounding the retinal pigmented epithelium. Moreover, primary cilium ablation in NCC also led to a decreased expression of Foxc1 and Pitx2, two transcription factors identified as major ASD causative genes. These findings suggest that primary cilia are indispensable for NCC to form normal AS structures via Hh signaling. Defects in primary cilia could, therefore, contribute to the pathogenesis of ASD, and to their complications such as congenital glaucoma.

developmental biology↗