Using hippocampal organoids to study human brain development

Research project

Human pluripotent stem cells can be guided to form neural organoids, so called mini-brains, self-organizing structures that mimic the morphology and molecular composition of early embryonic brains. Here, we develop human hippocampal organoids to study mechanisms of early hippocampal development and activity-dependent gene expression and circuit formation. Indeed, we observed significant co-clustering of RNA expression signatures between hippocampus-like organoids and the developing human hippocampus, as analyzed by single cells RNA-sequencing. Additional molecular and functional phenotyping is ongoing.

This project will provide a versatile tool to develop more complex organoids to model developmental brain connectivity between the hippocampus and other regions of the brain. It will set the foundation for future collaborative projects within the URPP groups. Establishing hippocampal organoids may be of substantial value for future research within the URPP that aims to bridge the current gap between experimental rodent work and human brain structure and function. 

Research groups

Principal investigators: Sebastian Jessberger, Csaba Földy, Fritjof Helmchen

PhD student: Daniel Gonzalez (until 08.2023), Linda Brandi

Publications

Denoth-Lippuner A, Royall LN, Gonzalez-Bohorquez D, Machado D, Jessberger S (2022) Injection and electroporation of plasmid DNA into human cortical organoids. STAR Protocols 3, 101129. 

Gonzalez-Bohorquez D, Gallego Lopez IM, Jaeger BN, Pfammatter S, Bowers M, Semenkovich CF, Jessberger S (2022)  FASN-dependent de novo lipogenesis is required for brain development. PNAS 119.

Underlined: AdaBD researchers