Objective To investigate the effect and mechanism of bilirubin on neural stem cell(NSC)viability and proliferation.Methods Primary mouse NSCs were cultured with different concentrations of bilirubin,and live-dead cell staining was performed after 2 days of culture;neurosphere assay,Ki-67 assay,and transcriptome sequencing were performed after 7 days of culture to in-vestigate the effects of bilirubin on NSC viability and proliferation.Results Approximately 1.71-6.84 μmol/L bilirubin had no effect on NSC viability,while 13.68 μmol/L bilirubin decreased NSC viability.Approximately 0.17-6.84 μmol/L bilirubin promo-ted NSC proliferation,while this pro-proliferation effect disappeared when the bilirubin concentration reached 13.68 μmol/L.Biliru-bin increased Ki-67 expression in NSCs.RNA Seq showed that bilirubin upregulated 184 genes and downregulated 100 genes.Gene Ontology analysis suggested that the differentially expressed genes were mainly related to"regulation of cell population proliferation"and other biological processes.KEGG analysis suggested that the differentially expressed genes were related to several pathways,such as the"PI3K-AKT signaling pathway".Conclusion High bilirubin concentrations were toxic to NSCs,while low bilirubin concentrations had no effect on NSC viability and promoted NSC proliferation.
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