ePoster

High-throughput neural connectivity mapping in human brain organoids

Abel Vertesy, Ramsey Najm, Balint Doleschall, Li Chong, Yoav Ben Simon, Juergen Knoblich
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Abel Vertesy, Ramsey Najm, Balint Doleschall, Li Chong, Yoav Ben Simon, Juergen Knoblich

Abstract

The human brain is an extremely complex network of ~80 billion neurons, and it underpins all thoughts and emotions through coordinated neural activity. The underlying network changes with age and environment, and it is vulnerable to perturbations. Our goal is to understand both normal and pathological neural networks at the level of individual neurons, and how human illnesses affect them.Studying human neurodevelopmental disorders is often challenging using animal models. By using cerebral organoids from induced pluripotent stem cells (iPS), we can investigate these conditions in sophisticated 3D tissue that is highly accessible and scalable. In order to understand how genetic perturbations alter gene expression and, in turn, connectivity, we must investigate both within the same cell.Advancements in electron microscopy have demonstrated remarkable precision in revealing cellular connectivity in tissues ranging from μm to mm. However, this method is not currently scalable to a range of 10s to 100s of conditions, nor can it directly establish a connection between gene expression and connectivity. To investigate both patterns, we have developed a barcoded single-cell connectome & transcriptome mapping method. Using multiple internal and external controls, we identified true connectivity patterns of thousands of neurons. In 120-150 day-old organoids, we link connectivity to transcriptional state and to tissue composition. We identified the distinct networks different cell types make, and how these connections evolve over time. We envision our high-throughput connectomics-by-sequencing as a complementary approach to existing techniques.

Unique ID: fens-24/high-throughput-neural-connectivity-85d0efe7