Gene profiling of HAX1-deficient iPSC-derived CD33-positive promyelocytes and their genetically corrected and wid-type counterparts

We investigated iPSC-derived granulopoiesis from Kostmann patients (HAX1-deficient iPSCs) and gene corrected isogenic lines generated by CRISPR-Cas9 gene editing. Utilizing neutrophilic differentiation assay, we have successfully modeled the Kostmann hematologic phenotype that is characterized by perturbed granulocytic differentiation and compensatory overproduction of monocytes. We demonstrate that targeted correction of the HAX1-mutation reestablished a HAX1 and HCLS1-centered transcription network in immature myeloid progenitors, which is involved in the regulation of apoptosis and also myeloid differentiation. HAX1-deficient iPSCs were genetically corrected by CRISPR technology. After neutrophilic in vitro differentiation assay, CD33-positive promyelocytes were purified by flow sorting. HAX1-deficient cells were compared to isogenic and wild-type cells.