Classification and pathological mechanisms of Craniosynostosis based on the differentiation pattern of iPS cells
Abstract: Craniosynostosis is defined as premature closure of one or more cranial sutures. It is suggested that the condition is induced by accelerated ossification leading to craniofacial skeletal deformities and compromise of cranial space for growing brain. Although it is a multifactorial disease with several risk factors including increased intracranial pressure, the involvement of genetic factors is strongly suggested. The current treatment is mainly surgical resection, and repeated surgeries are often required due to resynostosis. Therefore, prediction of clinical condition is important for treatment planning. However, currently reported gene mutations in craniosynostosis patients explain only 20% of all craniosynostosis cases.
The ability to predict the pathological transition not only facilitates the planning of treatment strategies but also the development of new therapies. Since it is currently impossible to classify patients based on genetic factors alone, we hypothesized that the expression pattern of osteogenic markers and craniosynostosis associated genes in osteobalsts could be used to classify craniosynostosis patients.
Cranial bone-derived osteoblast ossification capacity is known to change with age, therefore It is not easy to compare the pattern of expression of osteogenic markers among patient-derived osteoblasts and control osteoblasts directly.
It has been reported that iPS cells maintain an epigenetic state character from which they are derived, therefore they are prone to easily differentiate into the original cell type.
Using this feature, we will establish a system to establish patient osteoblast-derived iPS cells and redifferentiate them into osteoblasts to compare the expression patterns of osteogenic markers for patient classification.
Japanese Division Meeting
2020 Japanese Division Meeting (Virtual) Virtual, Japan
2020 SⅡ-3 Future is now! Stem cell revolution in hard and soft tissue engineering
( Section of Molecular Craniofacial Embryology, Tokyo Medical & Dental University Graduate School of Medical and Dental Sciences