GFI1B and LSD1 repress myeloid traits during megakaryocyte differentiation.

ABSTRACT: The transcription factor Growth Factor Independence 1B (GFI1B) recruits Lysine Specific Demethylase 1 A (LSD1/KDM1A) to stimulate gene programs relevant for megakaryocyte and platelet biology. Inherited pathogenic GFI1B variants result in thrombocytopenia and bleeding propensities with varying intensity. Whether these affect similar gene programs is unknow. Here we studied transcriptomic effects of four patient-derived GFI1B variants (GFI1B^T174N,^H181Y,^R184P,^Q287*) in MEG01 megakaryoblasts. Compared to normal GFI1B, each variant affected different gene programs with GFI1B^Q287* uniquely failing to repress myeloid traits. In line with this, single cell RNA-sequencing of induced pluripotent stem cell (iPSC)-derived megakaryocytes revealed

SUBMITTER: Venhuizen J 

PROVIDER: S-EPMC10978956 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature