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Review
. 2020 Feb 19;11(1):16.
doi: 10.1186/s13229-020-0320-2.

Recent advances in human stem cell-based modeling of Tuberous Sclerosis Complex

Wardiya Afshar Saber  1 , Mustafa Sahin  2
Affiliations
Review

Recent advances in human stem cell-based modeling of Tuberous Sclerosis Complex

Wardiya Afshar Saber et al. Mol Autism. .

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by epilepsy, intellectual disability, and benign tumors of the brain, heart, skin, and kidney. Animal models have contributed to our understanding of normal and abnormal human brain development, but the construction of models that accurately recapitulate a human pathology remains challenging. Recent advances in stem cell biology with the derivation of human-induced pluripotent stem cells (hiPSCs) from somatic cells from patients have opened new avenues to the study of TSC. This approach combined with gene-editing tools such as CRISPR/Cas9 offers the advantage of preserving patient-specific genetic background and the ability to generate isogenic controls by correcting a specific mutation. The patient cell line and the isogenic control can be differentiated into the cell type of interest to model various aspects of TSC. In this review, we discuss the remarkable capacity of these cells to be used as a model for TSC in two- and three-dimensional cultures, the potential variability in iPSC models, and highlight differences between findings reported to date.

Keywords: Astrocytes; Autism; Brain organoids; CRISPR/Cas9; Cortical tuber; Human pluripotent stem cells; Neurons; Purkinje neurons; Tuberous sclerosis complex.

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Conflict of interest statement

Mustafa Sahin has received research funding from Roche, Novartis, Pfizer, LAM Therapeutics, and Quadrant Biosciences and has served on the Scientific Advisory Board of Sage Therapeutics, Roche, Takeda, and PTEN Research Foundation.

Figures

Fig. 1
Fig. 1
Human neuronal models of TSC. Various approaches to generate cellular models of TSC with pluripotent stem cells. Somatic cells from TSC patients and parental control can be reprogrammed into pluripotent stem cells and differentiated in the cell type of interest to model neurological aspects of TSC. In gray, models that have not been yet published using isogenic controls
See this image and copyright information in PMC

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