Single-cell connectomics to understand human psychiatric diseases
Many psychiatric diseases are associated with defects in the connections between neurons. To understand these diseases, we need to know the number and type of connections a single neuron forms, and how these connections are affected in disease. The EU-funded PhenoConnectomics project aims to develop a connectome-by-sequencing assay to chart synaptic networks of thousands of neurons. Change in synaptic connectivity is the main characteristic of autistic disorders, such as Rett syndrome, caused by a mutation in the MECP2 gene, which controls gene expression and the formation of synaptic contacts. Researchers will study Rett syndrome on the transcriptional and connectivity levels using healthy and MECP2-deficient human cortical organoids. This study will establish single-cell connectivity as a disease phenotype, potentially leading to the early detection of psychiatric diseases.
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