Tuberous Sclerosis Complex (TSC)
Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is complex genetic disorder often associated with pharmacoresistant seizures, autism, and intellectual disability, characterized by the presence of anatomical malformations in brain as well as tumors in other organs.
Hypomelanotic macules (A). Facial angiofi bromas (B). Shagreen patch (C). Hyperechoic rhabdomyoma detected by echocardiography (D). Retinal hamartoma (E). Lymphangiomyomatosis (F). PMID: 18722871
Despite the clear involvement of mutations in either the TSC1 or TSC2 gene, it remains unknown just how TSC1/TSC2 deficiency ultimately leads to pharmacoresistant seizures and other cognitive comorbidities.
It is generally believed that seizures in TSC arise from cortical tubers, which are benign tumors in the brain characterized by the presence of large bizarre cells, called balloon cells and cytomegalic neurons.
However, whether or not these abnormal cells are “seizure-causing” appears to be an intractable question in the field, since rodent models do not develop the abnormal cell types and structure as seen in human TSC patients.
Ictal EEG showing epileptic spasms (A). Axial MRI showing cortical tubers in a 20-month-old boy (arrows) (B). PMID: 18722871
This TSC research project aims to tackle a seemingly intractable question by exploring the transcriptomic profile of cortical tubers.
Leveraging a wealth of surgically resected cortical tuber tissue available at our institutes, we employ high-throughput single-cell sequencing approaches and conduct a multi-modal analysis.
This allows us to capture the transcriptomic, electrophysiological, morphological, and spatial characteristics of individual cells.
Through this comprehensive strategy, we aim to deconvolute the complex cortical tuber tissue into distinct cellular subtypes.
The ultimate goal is to gain new insights into the underlying mechanisms of TSC and, potentially, to identify novel therapeutic targets.