Thanks to a newly developed calculation method, Luxembourg researchers can accurately predict how a subpopulation of cells can be transformed into another. "The method has great potential for regenerative medicine, for example when it comes to replacing lost cell subpopulations during the course of the disease," explains Prof. Dr. med. Antonio del Sol, head of the Computational Biology working group of the Luxembourg Center for Systems Biomedicine (LCSB) at the University of Luxembourg. In collaboration with Parkinson's researchers from the Karolinska Institute in Sweden, the scientists tested the practicality of their method: they showed that based on computer-aided predictions, stem cells from the brain could actually be reprogrammed and eventually converted into the desired subtype of neurons. The researchers presented their findings in the journal Nature Communications .
Identify Cell Types
Skin cells and neurons are not the same, so much is obvious from their consideration. But even cells of the same type can have subtle differences in genetic activity, which sometimes have a strong influence on their cellular function, resulting in different cell subpopulations or subtypes. For example, dopaminergic neurons are neurons in the brain that produce the neurotransmitter dopamine. During Parkinson's disease, these cells die in the substantia nigra of the midbrain ̵
To address this problem, del Sol and his team developed the TransSyn computer platform. His predictions are based on the gene expression programs of individual cells in a population. After a multi-stage computer pipeline, TransSyn looks for subtle differences between cell subtypes. The researchers know that there are always several synergistically interacting regulatory genes that work together to characterize a subtype. Once these synergistic "transcriptional nuclei" have been identified for each subtype, there is enough data to go to lab applications, for example, to convert one cell subtype into another. To this end, the scientists treat cell cultures with specific factors in order to change their gene expression profiles. These factors activate certain genes and disable others.
Cooperation with the Karolinska Institute
Based on the predictions made in Luxembourg, the researchers of the Swedish Karolinska Institute converted human neuroepithelial stem cells (hNES cells) from the Hindbrain into midbrain dopaminergic neuron progenitor cells to develop dopaminergic neurons. "This may prove to be a strategy for cell therapy in Parkinson's disease," claims del Sol.
Testing the predictions in the laboratory
The Luxembourg researchers are continuing to examine the applicability of their platform. for example in cooperation with the Gladstone Institute in the USA. The American researchers, under the direction of Deepak Srivastava, are looking for an efficient way to transform right ventricular heart cells into those of the left ventricle – and vice versa – because the two subtypes have subtle differences in their gene expression profiles and thus in their functional activity. "We already have the predictions, and our colleagues in the US will begin their experiments over the next few weeks," said Del Sol.
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