Organoids and neural progenitor cells development to study XPD-mutated trichothiodystrophy

• Grant number: 22/13690-4
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Effective date (Start): August 15, 2023
• Effective date (End): December 14, 2023
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Carlos Frederico Martins Menck
• Grantee: Vitória Rezende Goll
• Supervisor: Alysson Renato Muotri
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: University of California, San Diego (UC San Diego), United States
• Associated to the scholarship: 22/02400-5 - Evaluation of metabolic alterations in human cells from patients with Trichothiodystrophy with deficiency in nucleotide excision repair, BP.IC

Abstract

Trichothiodystrophy is a progeroid syndrome related to Nucleotide Excision Repair deficiency, derived from a mutation in the ERCC2/XPD gene. Considering that the most important and more complex clinical feature of TTD is the neurodegeneration process and that the available cells we have are patients' fibroblasts in monolayer culture, the possibility to use a more appropriate and complete model of study is needed. Recent studies have shown the potential use of induced pluripotent stem cells (iPSCs) to study molecular mechanisms of rare diseases and can also be differentiated into any type of cell, including neural progenitor cells. In addition, brain organoids developed from these iPSCs are a promising 3D model of study for neurodegeneration diseases due to their similarity to the neural tissue. Thus, this project has the objective to obtain tridimensional cerebral cortical organoids, from iPSC derived from XPD-mutated Trichothiodystrophy patients; developing neural progenitor cells (NPCs) from iPSC; and testing ultraviolet (UV) sensitivity patterns, oxidative stress, and cell cycle of iPSCs and NPCs. (AU)