SfN19: Brain organoids advance studies of neural development, research suggests

Written by Alex Hyde (Future Science Group)

Credit: Collin Edington and Iris Lee, Koch Institute MIT. CC BY-NC-ND

New research presented at SfN Neuroscience 2019 (19–23 October, Chicago, IL, USA) outlines some of the exciting developments and important limitations in the use of brain organoids.

“The advances presented today illustrate the exciting potential of using organoids to study brain processes in normal development and disease. However, we know they must be rigorously compared to the normally developing human brain to better understand their strengths and limitations,” commented Hongjun Song, a Professor at the University of Pennsylvania Perelman School of Medicine (PA, USA).

Brain organoids can consistently reproduce rich diversity of cell types found in human cerebral cortex, study indicates

Research presented by scientists based at Harvard University (MA, USA) has indicated that a sample of 21 brain organoids developed from different cell lines consistently reproduced the rich diversity of cell types that are present in the human cerebral cortex.

In the past, research using brain organoids has been limited by high organoid-to-organoid variability, raising questions about the accuracy and reproducibility of the gathered data. In this study, researchers carried out single-cell RNA sequencing of 166,242 cells isolated from 21 individual organoid models of the dorsal forebrain. The sequencing demonstrated that 95% of organoids generate a virtually indistinguishable corpus of cell types.

The results revealed organoid-to-organoid variability similar to that of individual endogenous brains. Within the abstract of the study, the scientists explain that their research indicates that: ‘…reproducible development of complex central nervous system cellular diversity does not require the context of the embryo.’

It is anticipated that such organoids can pave the way for modeling brain development and diseases that have not yet been experimentally accessible outside the embryo.

Abstract: Velasco S, Kedaigle AJ, Simmons SK et al. Individual brain organoids reproducibly generate cell diversity of the human cerebral cortex. Presented at: SfN Neuroscience, Chicago, IL, USA, 19–23 October 2019.

Using brain organoids, researchers reveal that the imbalance between excitation and inhibition could be an underlying basis for autism

Another study, from scientists based at the University of Maryland (MD, USA), has revealed that brain organoids that model early neural circuit development support the theory that an excitatory/inhibitory imbalance in the brain could form the underlying basis for autism.

It is well established that healthy brain function is maintained by a tight balance of excitatory and inhibitory neuronal activity and it is theorized that an imbalance leading to too much or too little firing could cause problems with learning and processing sensory information. Cellular phenotyping of neurons in people with autism has presented researchers with a major challenge.

In this research, scientists used serum-free embryoid bodies to create an ‘autism-in-a-dish’ model to reflect early circuit development in the human cortex. Compared with control organoids, those created from individuals with autism spectrum disorder tended to contain fewer inhibitory neurons.

Differences in the shape of excitatory neurons in the organoids created from individuals with autism spectrum disorder were also observed, with the team suggesting this could have implications on the number and type of connections formed.

The scientists concluded that this research demonstrates the technique’s ability to identify excitatory/inhibitory deficits and add that further research to evaluate the dynamics of GABA+ and VGLUT+ populations in autism spectrum condition-derived models is required.

Abstract: Durens M, Nestor J, Herold K et al. Human induced pluripotent stem cell-derived 3D organoids combined with high-content screening reveal network-level phenotypes in a subset of individuals with idiopathic autism. Presented at: SfN Neuroscience, Chicago, IL, USA, 19–23 October 2019.

Cell types within brain organoids may lack the cellular and structural integrity found in the developing cortex

Lastly, research presented by scientists based at the University of California San Francisco (CA, USA) highlights the importance of an objective approach towards the use of brain organoids in research and the necessity to be aware of the model’s limitations.

The presented research demonstrated that organoids do contain a rich diversity of cell types that appear to be broadly similar to those in the developing brain. However, single-cell RNA sequencing and complementary immunohistochemical analyses revealed the cell types contained in organoids often lack the cellular and structural integrity of genuine cells found in the developing context.

The scientists concluded that for the best utilization of these models a better definition of their limitations is required.

Abstract: Andres M, Bhaduri A, Kriegstein AR. Using organoid models to study human cortical development. Presented at: SfN Neuroscience, Chicago, IL, USA, 19–23 October 2019.

Source: Society for Neuroscience. “Brain in a dish” models advance studies of neural development and disease. Press release: www.sfn.org/Meetings/Neuroscience-2019

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