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To be able to explore early steps of human brain development, such as neural circuit formation and communication within cells, we are working on developing so-called brain organoids. Organoids are 3D structures that are grown from stem cells in a petri dish and mimic some of the properties of the corresponding human brain structures.
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 generate hippocampus-like organoids from human embryonic stem cells (hESCs) to study mechanisms of early hippocampal development and activity-dependent gene expression and circuit formation. With genetic approaches, we induced the formation of 3D structures that contain hippocampal-like neurons, such as granule cells. We are currently confirming their development using RNA sequencing and immunohistochemistry. Additionally, we have optimized experimental strategies to manipulate organelles in these organoids, further expanding their research potential.
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.
Principal investigators: Sebastian Jessberger, Csaba Földy, Fritjof Helmchen
PhD student: Daniel Gonzalez (until 08.2023), Linda Brandi
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
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
Underlined: AdaBD researchers