Oncogenic Gata1 causes stage-specific megakaryocyte differentiation delay.

Oncogenic Gata1 causes stage-specific megakaryocyte differentiation delay. Haematologica. 2020 Jun 11;: Authors: Juban G, Sakakini N, Chagraoui H, Cruz Hernandez D, Cheng Q, Soady K, Stoilova B, Garnett C, Waithe D, Otto G, Doondeea J, Usukhbayar B, Karkoulia E, Alexiou M, Strouboulis J, Morrissey E, Roberts I, Porcher C, Vyas P Abstract The megakaryocyte/erythroid Transient Myeloproliferative Disorder (TMD) in newborns with Down Syndrome (DS) occurs when N-terminal truncating mutations of the hemopoietic transcription factor GATA1, that produce GATA1short protein (GATA1s), are acquired early in development. Prior work has shown that murine GATA1s, by itself, causes a transient yolk sac myeloproliferative disorder. However, it is unclear where in the hemopoietic cellular hierarchy GATA1s exerts its effects to produce this myeloproliferative state. Here, through a detailed examination of hemopoiesis from murine GATA1s ES cells and GATA1s embryos we define defects in erythroid and megakaryocytic differentiation that occur relatively late in hemopoiesis. GATA1s causes an arrest late in erythroid differentiation in vivo, and even more profoundly in ES-cell derived cultures, with a marked reduction of Ter-119 cells and reduced erythroid gene expression. In megakaryopoiesis, GATA1s causes a differentiation delay at a specific stage, with accumulation of immature, kit-expressing CD41hi megakaryocytic cells. In this specific megakaryocytic c...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research