biostudies-literatureMakaryan VNHLBI NIH HHS98-112https://www.ebi.ac.uk/biostudies/studies/S-EPMC12439587biostudies-literatureUnknown7(3)Congenital neutropenia is characterized by a reduced neutrophil count, decreased innate immunity and increased susceptibility to recurrent infections. While congenital neutropenia has various genetic causes, recent studies have linked <i>TCIRG1</i> mutations to this condition. <i>TCIRG1</i>, a key component of the vacuolar ATPase (V-ATPase) complex, is essential for osteoclast function, but its role in hematopoiesis remains unclear. We previously identified heterozygous <i>TCIRG1</i> mutations, including R736S, R736C, R736P, and E722D, in individuals with congenital neutropenia. However, the mechanism by which these mutations lead to impaired granulopoiesis remains unknown. To investigate the functional consequences of <i>TCIRG1</i> mutations, we generated induced pluripotent stem cells (iJournal of cellular immunologyModeling <i>TCIRG1</i> Neutropenia by Utilizing Patient Derived Induced Pluripotent Stem Cells.PMC12439587R01 HL151629Bolyard AAMathieu JKelley MLDale DCHesson JMakaryan VLenaeus MJCavanaugh CfalseModeling <i>TCIRG1</i> Neutropenia by Utilizing Patient Derived Induced Pluripotent Stem Cells.Congenital neutropenia is characterized by a reduced neutrophil count, decreased innate immunity and increased susceptibility to recurrent infections. While congenital neutropenia has various genetic causes, recent studies have linked <i>TCIRG1</i> mutations to this condition. <i>TCIRG1</i>, a key component of the vacuolar ATPase (V-ATPase) complex, is essential for osteoclast function, but its role in hematopoiesis remains unclear. We previously identified heterozygous <i>TCIRG1</i> mutations, including R736S, R736C, R736P, and E722D, in individuals with congenital neutropenia. However, the mechanism by which these mutations lead to impaired granulopoiesis remains unknown. To investigate the functional consequences of <i>TCIRG1</i> mutations, we generated induced pluripotent stem cells (i2025-01-01T00:00:00Z20252026-06-03T03:00:39.327Z2026-04-23T03:13:35.958ZS-EPMC124395874096461410.33696/immunology.7.228