The loss of Nudt15 thiopurine detoxification enhances direct DNA damage in hematopoietic stem cells (HSCs)

The kinetics of HSCs after 6-MP administration were examined by flow cytometry analysis, and genes differentially expressed between HSCs from Nudt15+/+ mice and HSCs from Nudt15R138C/R138C mice were identified by RNA-sequencing before the appearance of 6-MP-induced HSC damage. HSCs extracted from Nudt15+/+ and Nudt15R138C/R138C mice treated with 6-MP were analyzed by comparative gene expression profiling using RNA-seq.

本研究通过流式细胞术分析，检测了6-巯嘌呤（6-MP）给药后造血干细胞（Hematopoietic Stem Cells，HSCs）的动力学变化；并在6-MP诱导的HSCs损伤出现前，通过RNA测序（RNA-sequencing）鉴定了Nudt15+/+小鼠与Nudt15R138C/R138C小鼠的HSCs之间的差异表达基因。此外，本研究还对经6-MP处理的Nudt15+/+及Nudt15R138C/R138C小鼠来源的HSCs，采用RNA测序（RNA-seq）开展了比较基因表达谱分析。