| dc.description.abstract | Background: While there is information on transcriptomic biomarkers of
demyelination, the heterogeneity in the methods and cell types/tissues used
makes it difficult to select transcriptomic biomarkers for demyelination studies.
In addition, there is scarce data on the crosstalk between microglia and
oligodendrocyte progenitor cells (OPCs), 2 of the 4 cell types involved in
demyelination/remyelination processes.
Objectives: To identify 1) transcriptomic biomarkers of demyelination in
microglia, OPCs and corpus callosum following a similar pipeline, and 2)
microglia ligands and OPC receptors and targets genes involved in the
microglia-OPC crosstalk.
Methods: Data were obtained from all available studies of gene expression
data by microarray in mice samples treated with cuprizone available at
GEO/Array Express. Differential expression analyses were performed to identify
transcriptomic biomarkers. The following pipeline was used: quality control,
normalization, annotation, gene filtering, aggregation, batch effect correction,
differential expression analysis, annotation, plotting and functional analysis. The
crosstalk analysis was performed with the NicheNet model for intercellular
communication using expressed genes in microglia and OPCs obtained from
the differential expression analysis. Ligand-target regulatory potentials, ligand receptor networks and ligand-receptor interactions were obtained from the
NicheNet model. Analyses were performed in R.
Results: There were 166, 12, and 2730 differential expressed genes (DEGs)
identified in the corpus callosum, microglia and OPC differential expression
analyses, respectively. DEGs included genes associated with demyelination
such as Ninj2, Lpl, and Mobp. DEGs identified in the corpus callosum and OPC
analyses were associated with GO terms and Wikipathways related to myelin.
There was 1 DEG identified in both the microglia and the OPCs analyses, and 95
DEGs identified in both the corpus callosum and OPCs analyses. We identified
45 potential ligands of microglia that could affect gene expression in OPCs, 115
DEGs in OPCs that were predicted target genes of these ligands, and 43
potential OPC receptors of the identified microglia ligands. Some of the
identified microglia ligands, and OPC receptors and targets genes, were
differentially expressed in cuprizone treated samples compared to control and
were associated with demyelination and myelin formation.
Conclusions: The differential expression pipeline was able to identify
transcriptomic biomarkers associated to demyelination in studies using different
platforms and cell types/tissues. The crosstalk analysis between microglia and
OPCs identified novel microglia ligands, and OPC receptors and target genes. | es |
