Researchers predict cell conversion factors

July 30, 2018, University of Luxembourg
Thanks to a newly developed computational method, Luxembourg researchers can accurately predict how one subpopulation of cells can be converted into another. Credit: University of Luxembourg

Thanks to a newly developed computational method, Luxembourg researchers can accurately predict how one subpopulation of cells can be converted into another. "The method has great potential for regenerative medicine when it comes to replacing cell subpopulations that have been lost in the course of disease, for example," explains Prof. Dr. Antonio del Sol, head of the Computational Biology group of the Luxembourg Centre for Systems Biomedicine (LCSB) at the University of Luxembourg. In collaboration with Parkinson's disease researchers at the Karolinska Institute, Sweden, the scientists showed that, based on computational predictions, neural stem cells can be reprogrammed and ultimately converted into a desired subtype of neurons. The researchers presented their results in the journal Nature Communications.

Skin and neurons are not the same. But even cells of the same type can have fine differences in genetic activity that sometimes have a powerful influence on their cellular function, giving rise to different cell subpopulations or subtypes. For example, dopaminergic neurons are nerve cells in the brain that produce the neurotransmitter dopamine. In the course of Parkinson's disease, these cells in the substantia nigra of the midbrain die off—but not all of them. Only one specific subtype of these cells dies off. "The identity of a particular cell subtype is characterised and maintained by a few interacting regulatory genes," del Sol explains. "Yet the differences between the subtypes are subtle and difficult to detect using the existing analytical methods."

In order to address this problem, del Sol and his team developed a computational platform called TransSyn. Its predictions are based on the gene expression programs of individual cells in a population. Following a multistep computational pipeline, TransSyn searches for subtle differences between cell subtypes. The researchers know there are always multiple, synergistically interacting regulatory genes working together to characterise a subtype. Once these synergistic 'transcriptional cores' have been identified for each subtype, there are enough data to move onto laboratory applications, such as converting one cell subtype into another. To do that, the scientists treat cell cultures with specific factors to alter their . These factors activate certain genes while deactivating others.

Working from the predictions made in Luxembourg, the researchers at the Swedish Karolinska Institute, converted human neuroepithelial stem cells (hNES cells) from the hindbrain into midbrain dopaminergic neuron progenitors capable of developing into . "This could prove to be a strategy for cell therapy in Parkinson's disease," del Sol asserts.

Testing the predictions in the lab

The Luxembourg researchers are continuing to test the applicability of their platform in collaboration with the Gladstone Institute in the U.S. The American researchers, led by Deepak Srivastava, are looking for an efficient way to convert heart cells of the right ventricle into those of the left ventricle and vice versa—because the two subtypes exhibit subtle differences in their gene expression profiles and thus functional activity. "We have the predictions already. Our colleagues in the U.S. will be starting their experiments in the next few weeks," del Sol said.

Explore further: New retinal ganglion cell subtypes emerge from single-cell RNA sequencing

More information: Satoshi Okawa et al, Transcriptional synergy as an emergent property defining cell subpopulation identity enables population shift, Nature Communications (2018). DOI: 10.1038/s41467-018-05016-8

Related Stories

Aggressive immune cells aggravate Parkinson's disease

July 20, 2018

Parkinson's disease, formerly referred to as "shaking palsy," is one of the most common disorders affecting movement and the nervous system. Medical researchers at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) ...

Brain tissue from a petri dish

April 13, 2017

The most complex organ in humans is the brain. Due to its complexity and, of course, for ethical reasons, it is extremely difficult to do scientific experiments on it - ones that could help us to understand neurodegenerative ...

Computational biology: Cells reprogrammed on the computer

July 31, 2013

Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have developed a model that makes predictions from which differentiated cells – for instance skin cells – can be very ...

Recommended for you

Study shows city rats eat better than country rats

October 17, 2018

A pair of researchers, one with Trent University in Canada, the other the University of Manchester in the U.K. has found evidence that rats living in cities have a much richer diet than rats living in the country. In their ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.