Precise Gene Editing Preserves Hematopoietic Stem Cell Function Following Transient p53-Mediate DNA Damage Response [bulk RNA-seq]

We evaluated transcriptional changes elicited by targeting AAVS1 and IL2RG genes and we found that the impact of one or few nuclease-induced DNA DSBs is minor and mainly limited to genes belonging to the p53 pathway. The same pathway was elicited by gene editing at two distinct genomic loci and was more pronounced in primitive vs. progenitor cells. Overall design: We analysed AAVS1 and IL2RG-edited cells 24h upon ZFN nucleases delivery on FACS-sorted “primitive” (CD34+ CD133+ CD90+) and “progenitor” (CD34+ CD133+ CD90-) cells from HSPC derived from 10 different donors. We performed the experiment in 3 biological replicate for a total of 18 samples analyzed. We then devided the samples according to the treatments (control monomers, DSB induced by IL2RG and AAVS1 ZFNs) and cells populations (primitive and progenitors).