Organoid model of the forebrain shows typical changes for autism
2021
Columbia University, New York, USA
Forebrain organoids generated from induced pluripotent stem cells of patients with symptomatic form of Autism Spectrum Disorder (ASD) with a mutation in CNTNAP2 were utilized, to study its effects on embryonic cortical development. Patients with this mutation present with clinical characteristics of brain overgrowth. Patient-derived forebrain organoids displayed an increase in volume and total cell number that is driven by increased neural progenitor proliferation. Single-cell RNA sequencing revealed PFC-excitatory neurons to be the key cell types expressing CNTNAP2. Gene ontology analysis of differentially expressed genes (DEgenes) corroborates aberrant cellular proliferation. Moreover, the DEgenes are enriched for ASD-associated genes. The cell-type-specific signature genes of the CNTNAP2-expressing neurons are associated with clinical phenotypes previously described in patients. The organoid overgrowth phenotypes were largely rescued after correction of the mutation using CRISPR-Cas9. This CNTNAP2-organoid model provides an opportunity for further mechanistic inquiry and the development of new therapeutic strategies for ASD.
Cortical overgrowth in a preclinical forebrain organoid model of CNTNAP2-associated autism spectrum disorder
Sander Markx, Bin Xu
Added on: 03-01-2022
[1] https://www.nature.com/articles/s41467-021-24358-4
