Transcriptome of erythroid cells derived from human CD34+ cells edited at the BCL11A erythroid enahncer or at the HBG1 and HBG2 promoters using CRISPR-Cas9

BCL11A represses gamma globin expression by binding to the gamma globin gene (HBG1 and HBG2) promoters. Genome editing of the BCL11A erythroid enhancer in the intron 2 of BCL11A gene or the BCL11A binding site at the HBG1/2 promoters disrupts this pathway and leads to gamma globin induction. Transcriptomic profiling of erythroid cells derived from human CD34+ cells edited at either target site using CRISPR-Cas9 revealed broader transcriptome perturbation when edited at the BCL11A erythroid enhancer. Human CD34+ cells were electroporated with CRISPR-Cas9 RNP targeting either the BCL11A erythroid enhancer or the HBG1/2 promoter BCL11A binding site. Unedited CD34+ cells were included as a control. CD34+ cells were placed in erythroid culture conditions for 11 days and their erythroid progenies were subjected to RNA-seq to evaluate transcriptome changes induced by editing at the either target site.