TY  - JOUR
A1  - Paranjapye, Alekh
A1  - Ahmad, Rili
A1  - Su, Steven
A1  - Waldman, Abraham J.
A1  - Phillips-Cremins, 
Jennifer E.
A1  - Zhang, Shuo
A1  - Korb, Erica
T1  - Autism spectrum disorder risk genes have convergent effects on transcription and neuronal firing patterns in primary neurons
Y1  - 2025/11/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 2433 
EP  - 2444 
DO  - 10.1101/gr.280698.125 
VL  - 35 
IS  - 11 
UR  - http://genome.cshlp.org/content/35/11/2433.abstract 
N2  - Autism spectrum disorder (ASD) is a highly heterogenous neurodevelopmental disorder with numerous genetic risk factors. Notably, a disproportionate number of risk genes encode transcription regulators including transcription factors and proteins that regulate chromatin. Here, we test the function of nine such ASD-linked transcription regulators by depleting them in primary cultured neurons. We then define the resulting gene expression disruptions using RNA sequencing and test effects on neuronal firing using multielectrode array recordings. We identify shared gene expression signatures across many ASD risk genes that converge on the disruption of critical synaptic genes. Fitting with this, we detect robust disruptions to neuronal firing throughout neuronal maturation. Together, these findings provide evidence that the loss of multiple ASD-linked transcriptional regulators disrupts transcription of synaptic genes and has convergent effects on neuronal firing that may contribute to enhanced ASD risk. 
ER  -