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Project

Transcriptional circuitry of patterning of neural tube organoids and in vivo spinal cord

Neural tube defects (NTD) are anomalies of central nervous system development that are associated with physical problems and/or intellectual disabilities. Through animal models more than 200 genes have been identified to be involved in NTD. Environmental factors also play an important role as shown by the impact of folic acid on NTD prevalence. Unfortunately animal models do not fully recapitulate human NTD phenotype and a human neural tube model is lacking. Recently a spina bifida aperta (SBA) cell model was established, SBA being a severe type of NTD. While cell models are useful they do not recapitulate the complexity and patterning of the spinal cord. Using organoids, 3D self-organizing structures, it is possible to recreate more complex tissue that can model NTD with more accuracy. In this project we propose to create a model using hPSCs that can recapitulate patterning of the developing spinal cord. Using a biomimetic extracellular matrix we can finetune optimal pattern and growing conditions. We will then further characterize the human neural tube-like organoid (hNTO) using single cell RNA sequencing (scRNA-seq), which will enable us to investigate cellular composition and underlying genetic mechanisms of the NTOs. This will be beneficial to validate the hNTO and spina bifida model and further investigate the underlying mechanisms of NTDs. Taken together, a robust neural tube model will provide opportunity investigate mechanisms of disease in human in high resolution.

Date:1 Feb 2019 →  30 Jun 2023
Keywords:Neural Tube Defects, Organoids, Spina Bifida Aperta, Single Cell RNA sequencing, Biomimetic matrices
Disciplines:Bioinformatics data integration and network biology, Tissue engineering
Project type:PhD project