Dual role of EZH2 on megakaryocyte differentiation, analysis at different stages of maturation at day 9 of culture

ABSTRACT: EZH2, the enzymatic component of PRC2, has been identified as a key factor in hematopoiesis. EZH2 loss of function mutations have been found in myeloproliferative neoplasms, more particularly in myelofibrosis, but the precise function of EZH2 in megakaryopoiesis is not fully delineated. Here, we show that EZH2 inhibition by small molecules and shRNA induces MK commitment by accelerating lineage marker acquisition without change in proliferation. Later in differentiation, EZH2 inhibition blocks proliferation and endomitosis and decreases proplatelet formation. EZH2 inhibitors similarly reduce polyploidization and proplatelet formation of JAK2V617F MK. In transcriptome profiling, the defect in proplatelet formation was associated with an aberrant actin cytoskeleton regulation pathway, wherea

ORGANISM(S): Homo sapiens

SUBMITTER: Dessen Philippe 

PROVIDER: E-MTAB-8610 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress