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Phenotyping of neurodevelopmental and psychiatric disorders with human iPSC-derived dopaminergic neurons
July 8, 2021 | 5pm (CET), 8am (PST), 11am (EDT)
Host
Dr. Marie Obien
VP Marketing and Sales at MaxWell Biosystems
Speaker
Speaker
Dr. Maria Sundberg
Research Fellow, Group of Prof. Sahin, Boston Children’s Hospital
Hannah Pinson
PhD Candidate, Group of Prof. Ginis, Vrije Universiteit Brussel & Visitor in Prof. Tegmark group, MIT
Abstract:
In recent years, the genetic causes of autism and schizophrenia have been studied intensively. In addition to monogenic deficits, deletions or duplications of specific chromosomal loci have also been associated with neurodevelopmental and psychiatric disorders. One of these regions is 16p11.2, which contains 29 protein coding genes, most of which are also expressed in the brain. Clinical studies have shown that deletion of 16p11.2 leads to severe developmental deficits, intellectual disability, and autism. On the other hand, patients with duplication of 16p11.2 locus have an increased risk of developing schizophrenia, bipolar disorder, depression and autism. Deficits in the dopamine signaling can cause behavioral problems and deficits in social interactions in the patients with autism and schizophrenia.
In this webinar, our speakers will:
- Speak about how they studied the effects of 16p11.2 copy number variations on dopamine signaling by differentiating human iPSCs, with either a 16p11.2 duplication or deletion, into dopaminergic (DA) neurons in vitro and how they characterized molecular and functional phenotypes of these neurons compared to healthy control neurons.
- Present their assessment of network activity using MaxOne, MaxWell’s high-density micro-electrode array (MEA) platform and with multi-well low-density MEA. To analyze the transcriptional gene expression changes in the DA neurons, RNA sequencing was performed.
- Discuss their results: They detected that the cells carrying 16p11.2 deletion had an increased soma size, increased synaptic marker expression, and hyperactive DA-neuron networks compared to healthy control DA-neurons. Increased RhoA expression was also detected in the 16p11.2 deletion DA-neurons. Treatment of the neurons with a specific RhoA pathway inhibitor, Rhosin, rescued the network hyperactivation and the abnormal morphological development of the DA-neurons with 16p11.2 deletion. These results show that inhibition of RhoA pathway can serve as a potential therapeutic target for neurodevelopmental and neuropsychiatric disorders associated with 16p11.2 deletion.