Pharmacogenomics identification of small bioactive molecules for promoting oligodendrogenesis in a model of neonatal brain injury. – NeoRepair

Preterm birth is a public health concern, with many surviving children developing cognitive and behavioral deficits implying a strong social and economic burden for society. Both in humans and rodents, the developmental period around birth is a time of active generation of oligodendrocytes, myelination, and axonal organization that if strongly perturbed in many preterm children. Our goal is on one hand to characterize the main regulators of gene networks promoting oligodendrogenesis and on the other hand to find small molecules impacting these gene networks in regenerative contexts. To decipher the transcriptional control of postnatal oligodendrogenesis, we will combine unique transcriptional datasets from partner 1 and partner 2 laboratories with published genome wide dataset of chromatin marks, to identify co-regulated gene-networks specific for oligodendroglia. This will a allow refining a pharmacogenetic analysis recently published by partner 2, to identify molecules fostering oligodendrogenesis. Finally, with the help of partner 3, we will select the small bioactive molecules having the highest therapeutic potential and test them in a model of premature brain injury.