The Roles Of THAP11in Hematopietic Differntiation

THAP11is the most recently described member of THAP proteins and previousstudies suggested that THAP11was a transcription factor involved in cell growth,embryogenesis and ES cell pluripotency. Our previous study suggested that THAP11was a suppressor of c-Myc by binding directly to the promoter of c-Myc andrepressing the transcription of c-Myc. Various studies suggested that c-Myc was a keytranscription factor involved in erythroid-megakaryocytic fate decision. Furthermore,THAP11is expressed highly in human hematopoietic stem cells, multipotentprecursors and human umilical cord CD34+CD38-cells. However, no study has beenreported about the roles of THAP11in hematopoietic differentiation.In this study, we investigated the roles of THAP11on hematopoieticdifferenatiation. First, the expression profiles of THAP11during erythroid andmegakaryocytic differentiation were deceted. We found that THAP11wasdown-regulated during erythroid differentiation and increased during megakaryocyticdifferentiation. To further provide direct evidence for the roles of THAP11inhematopoietic differentiation, we constructed lentiviral vectors containing humanTHAP11gene or interfering sequence against THAP11, produced the lentivirusgranules containing or interfering human THAP11gene and established K562andTF-1cells stablely overexpressing or silencing THAP11by THAP11or siTHAP11lentiviral infections. K562cells were induced to erythroid differentiation with heminand TF-1cells were induced to erythroid differentiation with EPO. Overexpression ofTHAP11suppressed the accumulation of hemoglobin, GPA and HBA duringerythroid differentiation, while the downregulation of THAP11accelerated theiraccumulation. Furthermore, K562cells were induced to megakaryocyticdifferentiaiton with PMA and overexpression of THAP11in K562cells enhancedexpression of megakaryocytic lineage marker CD61and inreased numbers ofpolyploidization, while the downregulation of THAP11inhibited expression of CD61.In THAP11-K562cells during PMA-induced megakaryocytic differentiation,GATA-2and Fli1were up-regulated while c-Myc and c-Myb were down-regulated,which indicated that THAP11regulated erythroid-megakaryocytic differentiation,probably by modifying the expression levels of several key hematopoietictranscription factors.In addition, knockdown of THAP11in human cord blood CD34+cells led to increased cell growth, suggesting a potential role of THAP11inhematopoietic proliferation. Taken together, all the results suggested that THAP11was a negative regulator oferythoid differentiation and played a positive role in megakaryocytic differentiation.