It is now possible to accurately predict how one subpopulation of cells can be converted into another thanks to a new computational method, according to Luxembourg researchers.
Regenerative medicine
“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,” explained Prof. Antonio del Sol, head of the Computational Biology group of the Luxembourg Centre for Systems Biomedicine (LCSB) at the University of Luxembourg.
The practical feasibility of the method was tested through a collaborative effort with Parkinson’s disease researchers. In this work, it was demonstrated that based on computational predictions, stem cells from the brain could be reprogrammed and ultimately converted into the desired subtype of neurons. This work has been presented in Nature Communications.
Cells, even those of the same type, can have different genetic activities. These differences can impact their cellular function hugely, which in turn gives rise to different cell subpopulations or subtypes. An example of this is dopaminergic neurons, which are present in the brain and produce the neurotransmitter dopamine. During the course of Parkinson’s disease, cells in the substantia nigra of the midbrain die off, however, not all of them do. In fact, only one subtype of these cells actually 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.”
To address this issue, del Sol and his team developed the computational platform ‘TransSyn’, which uses the gene expression programmes of individual cells in a population to make predictions.
TransSyn follows a multistep computational pipeline to search for subtle differences between cell subtypes. As it is known that there are always multiple, synergistically interacting regulatory genes that work together to characterise a subtype, ‘transcriptional cores’ can be identified for each subtype. Then there is enough data to convert one cell subtype to another, which is done by treating cell cultures with specific factors to alter their gene expression profiles.
Using the predictions that had been made in Luxembourg, the researchers at the Swedish Karolinska Institutet, converted human neuroepithelial stem cells (hNES cells) from the hindbrain into midbrain dopaminergic neuron progenitors capable of developing into dopaminergic neurons. “This could prove to be a strategy for cell therapy in Parkinson’s disease,” del Sol stated.
The applicability of the platform is being tested in other collaborative work with other institutes.