In homeostatic conditions, MKs via TGFβ1 restrain stem cells and erythropoiesis with moderate ERB apoptosis that can be prevented by EPO to increase RBC production. Genetic or pharmacologic blockade of TGFβ1 awakens quiescent stem cells and unleashes erythropoiesis but in an ineffective way with major apoptosis. EPO administration may prevent apoptosis and lead to major RBC production. Many questions remain to investigate in order to fully understand this regulatory process.