Brain organoids 'made in Austria' resemble original to a great extent

December 20, 2016

Scientists find striking similarities in function, structure and even epigenetic features.

Fluorescent cross-section of a cerebral organoid

 Already in 2013 IMBA scientists have astonished the scientific community by being the first ones to grow a three dimensional organ model of the human brain. Tiny “brain-like” structures also called cerebral organoids, were grown in a special cell culture using human stem cells. In less than a month, the stem cells are able to grow into cell structures of up to 3 to 4 millimeters and contain structures that correspond to most of the regions of the brain. Not only do they reveal astounding insights into structure and function of the most important organ of the human body, cerebral organoids also allow the observation of early stage brain development to a remarkable degree.

Since the discovery of this novel method, cerebral organoids from Vienna have been used by many research labs to study development and diseases as it recapitulates early human brain development in vitro. Using the lab grown brain organoids scientists were able to model the development of human neuronal disorders like Alzheimer’s, Parkinson’s, Zika and Schizophrenia and identify their origin – opening up routes to long hoped-for model systems of the human brain.

“The complexity of the human brain has made it difficult to study many brain disorders in model organisms. Finding a technique that recapitulates human brain development in a dish has huge potential for basic research, but also for the pharmaceutical industry. Organoids could allow testing of therapies against brain defects and other neuronal disorders. Furthermore, they could enable the analysis of the effects that specific chemicals have on brain development," Jürgen Knoblich, Deputy Scientific director of IMBA explains. 

First epigenetic screening of organoids
In a recent study published in Cell reports, scientists have now compared cerebral organoids to real brains and found striking similarities in structure and functionality. For the very first time the epigenome of the organ model was sequenced. The epigenetic pattern of the DNA consists of chemical markers - little methyl groups - that are responsible for activating and silencing genes. These epigenetic traits act one layer above the DNA and are influenced by environmental factors like diet or stress. They have been increasingly tied to development and diseases like Schizophrenia, Alzheimer’s, or Parkinson’s.

Scientists found that even though epigenetic features of lab-grown organoids differ from real brains, their share some similar patterns. One possible explanation could be that in vitro grown cells are exposed to different environmental factors than an organ embedded in a system. However, similarity in epigenetic traits could be taken as useful measure of how similar a model is to the real brain. “By using the epigenetic pattern as a gauge we can get organoids even closer to the real brain. That would allow researchers to simulate brain development more accurately,” concludes last author John Ecker from the Salk Institute in La Jolla, California.

Original publication:
Cerebral organoids recapitulate epigenomic signatures of human fetal brain. Chongyuan Luo, Madeline A. Lancaster, Rosa Castanon, Joseph R. Nery, Juergen A. Knoblich, and Joseph R. Ecker. Cell Reports 

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