Differentiation of stem cells from human exfoliated deciduous teeth (SHED) of patients with Treacher Collins syndrome into neural crest cells and the elucidative potential of transcriptome analysis.

• Grant number: 24/23392-6
• Support Opportunities: Scholarships abroad - Research
• Start date: August 15, 2025
• End date: August 14, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Carlos Ferreira dos Santos
• Grantee: Carlos Ferreira dos Santos
• Host Investigator: Mingyu Liang
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Institution abroad: University of Arizona, United States

Abstract

A rare genetic condition known as Treacher Collins Syndrome (TCS) mostly affects the development of the craniofacial region, resulting in a variety of physical abnormalities such lower eyelid colobomas, external ear deformities, and mandibular and zygomatic hypoplasia. These abnormalities impede ribosome biogenesis and neural crest cell (NCC) development during embryogenesis. They are primarily brought on by mutations in the TCOF1 gene, with mutations in POLR1A, POLR1B, POLR1C, and POLR1D occurring less commonly. Derived from the ectoderm, NCC are multipotent and essential for craniofacial skeleton creation. The distinctive craniofacial abnormalities seen in TCS are caused by dysregulated NCC migration and differentiation. Because of their strong proliferation capacity and neural crest-like characteristics, stem cells from human exfoliated deciduous teeth (SHED) provide a viable in vitro model to investigate TCS etiology. The purpose of this study is to examine how SHED differentiates into NCC-like cells in order to look into their developmental flexibility and similarity to naturally occurring NCC derivatives. These differentiated cells' transcriptomes will reveal gene networks and biological pathways that have been upset by mutations linked to TCS, emphasizing variations in gene expression that could be a factor in craniofacial deformities. Furthermore, a thorough genetic landscape of TCS will be provided by complete genetic analyses of the aforementioned genes of SHED donors from both TCS-affected and non-syndromic individual. The results of such genetic analyses may help uncover pathogenic variations and support improvements in diagnosis and treatment. It is anticipated that this integrated method, which combines transcriptomics, complete genes analysis, and SHED-derived NCC models, would increase diagnostic accuracy for this crippling condition, uncover new treatment targets, and further our understanding of TCS molecular mechanisms, which would be of major importance to the treatments provided by our Hospital for Rehabilitation of Craniofacial Anomalies of the University of São Paulo (HRAC-USP), "Centrinho" in Bauru, to a large number of patients affected by TCS.