The Akt–mTOR network at the interface of hematopoietic stem cell homeostasis

Hematopoietic stem cells (HSCs) are immature blood cells that exhibit multilineage differentiation capacity. Homeostasis is critical for HSC potential and lifelong hematopoiesis, and HSC homeostasis is tightly governed by both intrinsic molecular networks and microenvironmental signals. The evolutionarily conserved serine/threonine protein kinase B (PKB, also referred to as Akt)–mammalian target of rapamycin (mTOR) pathway is universal to nearly all multicellular organisms and plays an integral role in most cellular processes. Emerging evidence has revealed a central role of the Akt–mTOR network in HSC homeostasis, because it responds to multiple intracellular and extracellular signals and regulates various downstream targets, eventually affecting several cellular processes, including the cell cycle, mitochondrial metabolism, and protein synthesis. Dysregulated Akt–mTOR signaling greatly affects HSC self-renewal, maintenance, differentiation, survival, autophagy, and aging, as well as transformation of HSCs to leukemia stem cells. Here, we review recent works and provide an advanced understanding of how the Akt–mTOR network regulates HSC homeostasis, thus offering insights into future clinical applications.