Reduced myeloid commitment and increased uptake by macrophages of stem cell-derived HPS2 neutrophils.

ABSTRACT: Hermansky-Pudlak syndrome type 2 (HPS2) is a rare autosomal recessive disorder, caused by mutations in the AP3B1 gene, encoding the β3A subunit of the adapter protein complex 3. This results in mis-sorting of proteins within the cell. A clinical feature of HPS2 is severe neutropenia. Current HPS2 animal models do not recapitulate the human disease. Hence, we used induced pluripotent stem cells (iPSCs) of an HPS2 patient to study granulopoiesis. Development into CD15^POS cells was reduced, but HPS2-derived CD15^POS cells differentiated into segmented CD11b⁺CD16^hi neutrophils. These HPS2 neutrophils phenocopied their circulating counterparts showing increased CD63 expression, impaired degranulation capacity, and intact NADPH oxidase activity.

SUBMITTER: Webbers SD 

PROVIDER: S-EPMC10796564 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature