Project description:Adult and fetal megakaryocytes are morphologically different. These differences contribute to neonatal thrombocytopenia in premature neonates and in neonates after infection and also contribute to poor megakaryocytes engraftment after umbilical cord blood transplant. We found that Dyrk1a kinase inhibition shift the fetal megakaryocytes phenotype toward adult phenotype. This effect is mediated by MKL1 the master regulator of megakaryocytes morphogenesis. To identify differences between adult and fetal megakaryocytes we performed RNA seq of adult derived megakaryocytes and fetal derived megakaryocytes treated and untreated with Dyrk inhibitors. Through this approach we identified cohorts of genes co-regulated in adult megakaryocytes and fetal megakaryocytes treated with the dyrk inhibitors. More importantly, we found that the dyrk inhibition in fetal megakaryocytes leads to upregulation of a significant number of MKL1 target genes.
Project description:Adult and fetal megakaryocytes are morphologically different. These differences contribute to neonatal thrombocytopenia in premature neonates and in neonates after infection and also contribute to poor megakaryocytes engrafment after umbilical cord blood transplant. We found that Dyrk1a kinase inhibition shift the fetal megakaryocytes phenotype toward adult phenotype. This effect is mediated by MKL1 the master regulator of megakaryocytes morphogenesis. To identify deferences between adult and fetal megakaryocytes we performed RNA seq of adult derived megakaryocytes and fetal derived megakaryocytes treated and untreated with Dyrk inhibitors. Through this approach we identified cohorts of genes co-regulated in adult megakaryocytes and fetal megakaryoctes treated with the dyrk inhibitors. More importantly, we found that the dyrk inhibition in fetal megakaryocytes leads to upregulation of a significant number of MKL1 target genes.