İnsan indüklenmiş pluripotent kök hücre kaynaklı lakrimal bez organoidlerinin metabolomik analizi

The lacrimal gland (LG), commonly known as the tear gland, regulates the ocular surface's homeostasis by secreting proteins and electrolytes that form the tear film's aqueous layer. It produces lacrimal fluid, which lubricates and protects the eye as the major exocrine gland of the eye. Loss of function brought on by LG damage has a negative impact on eye health and visual quality. Studies on human LG formation and development are few, despite the fact that a large percentage of the human population suffers from eye diseases caused by functional disorders in the LG, such as dry eye disease. The LG's structure and morphology at the molecular level are not well known in the literature. In this study, human induced pluripotent stem cells (hiPSCs) were differentiated into cells with characteristics of LG in vitro by recapitulating functional and mature LG morphology at different time points. Differentiation was carried out according to the protocol developed by our lab in previous studies. Additionally, LG's reaction was monitored upon forskolin stimulation to understand secretion functionality better. In this context, different maturation levels and secretion functionality of LG's upon forskolin stimulation were examined by untargeted gas chromatography-mass spectrometry (GC-MS) metabolomics. The results suggest that the metabolome of LG organoids changed significantly at different maturation levels and upon stimulation with different small molecules. In addition, different –omic analyzes can be performed on the produced LG organoids and can be integrated with other -omic analyzes to investigate LG organoids at the multi-omics level.