Autophagy is essential for human myelopoiesis

Emergency myelopoiesis (EM) is essential in immune defense against pathogens for rapid replenishing of mature myeloid cells. During the EM process, a rapid cell-cycle switch from the quiescent hematopoietic stem cells (HSCs) to highly proliferative myeloid progenitors (MPs) is critical. How the rapid proliferation of MPs during EM is regulated remains poorly understood. Here, we reveal that ATG7, a critical autophagy factor, is essential for the rapid proliferation of MPs during human myelopoiesis. Peripheral blood (PB)-mobilized hematopoietic stem/progenitor cells (HSPCs) with ATG7 knockdown or HSPCs derived from ATG7−/− human embryonic stem cells (hESCs) exhibit severe defect in proliferation during fate transition from HSPCs to MPs. Mechanistically, we show that ATG7 deficiency reduces p53 localization in lysosome for a potential autophagy-mediated degradation. Together, we reveal a previously unrecognized role of autophagy to regulate p53 for a rapid proliferation of MPs in human myelopoiesis. •Autophagy is essential for the rapid proliferation of MPs in human myelopoiesis•ATG7 deficiency reduces autophagy-mediated p53 degradation in MPs In this article, Pan and colleagues show that ATG7, a critical autophagy factor, is essential for the rapid proliferation of MPs derived from PB-HSPCs or hESCs-HSPCs during human myelopoiesis. Mechanistically, p53 protein is associated with LC3B, an important adaptor interacting with cargoes in autophagosomes, and ATG7 deficiency reduces p53 localization in lysosome for a potential autophagy-mediated degradation.