Erythropoiesis is a multi-step process of hematopoietic stem cells differentiation into red blood cells. At the end of terminal erythroid differentiation, the erythroblast expels its nucleus, giving rise to a reticulocyte and a membrane bound nucleus. This process is termed enucleation and is imperative to the maturation of red blood cell, in which the reticulocyte enters the blood stream and matures into functional erythrocyte. The erythrocyte has a major role in oxygen transport across body cells to enable gas exchange for proper cellular function. With the increasing demand of blood supply, the ability to produce functional in vitro erythrocytes is an appealing approach. However, despite advancement in the current culturing system, the enucleation process remains one of the bottle necks in transfusion medicine.
Through a chemical screen, we have recently identified CDK9 as a novel target required for enucleation of mouse erythroblasts. To understand how CDK9 is required for enucleation, and erythropoiesis at large, we have used a combination of biochemical, imaging and in vivo RNAi approaches in the mouse together with chemical genetics and CRISPR approaches in a human erythroid differentiation system. Here I will present my analysis of CDK9 in mouse erythropoiesis.