RNA-seq of granulocytes derived from control and AK2 depleted human HSPCs

Reticular Dysgenesis (RD) is a rare but devastating form of severe combined immunodeficiency, characterized by a maturation arrest of the myeloid and lymphoid lineages paired with sensorineural hearing loss. RD is caused by biallelic loss-of-function mutations in the mitochondrial enzyme adenylate kinase 2 (AK2). To study the effect of AK2 depletion on HSPC differentiation, we developed a biallelic AK2 CRISPR knock-out model using human HSPCs. AK2 depleted HSPCs display severe proliferation and myeloid differentiation defects, recapitulating RD patient phenotype. AK2 and AAVS1 (safe harbor control) knock-out HSPCs were differentiated along the granulocytic lineage and cells at different maturation stages were FACS sorted