Complement C4 Is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects
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In recent years, accumulating evidence has shown that the innate immune complement system is
involved in several aspects of normal brain development and in neurodevelopmental disorders,
including autism spectrum disorder (ASD). Although abnormal expression of complement components
was observed in post-mortem brain samples from individuals with ASD, little is known about the
expression patterns of complement molecules in distinct cell types in the developing autistic
brain. In the present study, we characterized the mRNA and protein expression profiles of a wide
range of complement system components, receptors and regulators in induced pluripotent stem cell
(iPSC)-derived neural progenitor cells, neurons and astrocytes of individuals with ASD and
neurotypical controls, which constitute in vitro cellular models that recapitulate certain
features of both human brain development and ASD pathophysiology. We observed that all the
analyzed cell lines constitutively express several key complement molecules. Interestingly,
using different quantification strategies, we found that complement C4 mRNA and protein are
expressed in significantly lower levels by astrocytes derived from ASD individuals compared to
control astrocytes. As astrocytes participate in synapse elimination, and diminished C4 levels
have been linked to defective synaptic pruning, our findings may contribute to an increased
understanding of the atypically enhanced brain connectivity in ASD.
Keywords: autism spectrum disorder; complement C4; complement system; iPSC-derived astrocytes;
synaptic pruning.
Reference
Mansur, F., e Silva, A. L. T., Santos-Gomes, A. K., Magdalon, J., de Souza, J. S., Griesi-Oliveira, K., ... & Sertie, A. L. (2021). Complement C4 is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects.
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