Complement C4 Is Reduced in iPSC-Derived Astrocytes of Autism Spectrum Disorder Subjects

• Published in: International journal of molecular sciences Vol. 22; no. 14; p. 7579
• Main Authors: Mansur, Fernanda, Teles e Silva, André Luiz, Gomes, Ana Karolyne Santos, Magdalon, Juliana, de Souza, Janaina Sena, Griesi-Oliveira, Karina, Passos-Bueno, Maria Rita, Sertié, Andréa Laurato
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 15-07-2021; MDPI
• Subjects: Astrocytes; Autism; autism spectrum disorder; Brain; Cell lines; Complement; complement C4; Complement component C4; Complement system; Gene expression; iPSC-derived astrocytes; mRNA; Neural networks; Neural stem cells; Neurodevelopmental disorders; Pluripotency; Progenitor cells; Proteins; Sample size; Stem cells; Synapse elimination; synaptic pruning
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22147579

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.