Metabolic sensor O-GlcNAcylation regulates megakaryopoiesis and thrombopoiesis through c-Myc stabilization and integrin perturbation.

ABSTRACT: Metabolic state of hematopoietic stem cells (HSCs) is an important regulator of self-renewal and lineage-specific differentiation. Posttranslational modification of proteins via O-GlcNAcylation is an ideal metabolic sensor, but how it contributes to megakaryopoiesis and thrombopoiesis remains unknown. Here, we reveal for the first time that cellular O-GlcNAcylation levels decline along the course of megakaryocyte (MK) differentiation from human-derived hematopoietic stem and progenitor cells (HSPCs). Inhibition of O-GlcNAc transferase (OGT) that catalyzes O-GlcNAcylation prolongedly decreases O-GlcNAcylation and induces the acquisition of CD34⁺ CD41a⁺ MK-like progenitors and its progeny CD34^- CD41a⁺ /CD42b⁺ megakaryoblasts (MBs)/MKs fr

SUBMITTER: Luanpitpong S 

PROVIDER: S-EPMC8248081 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature