Transient inhibition of JNK pathway improves hematopoietic stem cell engraftment

We found that transient inhibition of JNK pathway increased short term-HSC frequency in cord blood CD34+ cells by 12.56 folds. Transcriptome analysis shows that inhibition of JNK pathway upregulated HSC-specific and anti-oxidative gene expression, prevented upregulation of cell cycle entry, oxidative phosphorylation and glycolysis related gene expression, and downregulated reactive oxygen species (ROS) active gene expression. Consistently, cell cycle and metabolic analysis show that inhibition of JNK pathway prevented HSC from cell cycle entry, glucose uptake increase and ROS accumulation. Accordingly, transient inhibition of JNK pathway also enhanced long term-HSC recovery during cord blood CD34+ cell collection. Collectively, these findings suggest that transient inhibition of JNK pathway could promote quiescent state of HSCs by preventing cell cycle entry and metabolic activation, thus improving HSC recovery and engraftment ability. Overall design: RNA-seq analysis of 3 different cell samples: uncultured cord blood CD34+ cells, cord blood CD34+ cells cultured with DMSO for 24 h, and cord blood CD34+ cells cultured with JNK-IN-8 for 24 h