Impaired neurogenesis and neural progenitor fate choice in a human stem cell model of SETBP1 disorder.

ABSTRACT:

Background

Disruptions of SETBP1 (SET binding protein 1) on 18q12.3 by heterozygous gene deletion or loss-of-function variants cause SETBP1 disorder. Clinical features are frequently associated with moderate to severe intellectual disability, autistic traits and speech and motor delays. Despite the association of SETBP1 with neurodevelopmental disorders, little is known about its role in brain development.

Methods

Using CRISPR/Cas9 genome editing technology, we generated a SETBP1 deletion model in human embryonic stem cells (hESCs) and examined the effects of SETBP1-deficiency in neural progenitors (NPCs) and neurons derived from these stem cells using a battery of cellular assays, genome-wide transcriptomic profiling and drug-based phenotypic rescue.

Results

Neural i

SUBMITTER: Cardo LF 

PROVIDER: S-EPMC9940404 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature