HEMATOPOIESIS: Edited by Hal E Broxmeyer and Maegan L CapitanoSymmetric and asymmetric activation of hematopoietic stem cellsLoeffler, Dirk; Schroeder, TimmAuthor Information Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland Correspondence to Timm Schroeder, Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Mattenstrasse 26, 4058 Basel, Switzerland. Tel: +41 61 387 3392; e-mail: [email protected] Current Opinion in Hematology: July 2021 - Volume 28 - Issue 4 - p 262-268 doi: 10.1097/MOH.0000000000000644 Buy Metrics Abstract Purpose of review Hematopoietic stem cells (HSCs) are in an inactive quiescent state for most of their life. To replenish the blood system in homeostasis and after injury, they activate and divide. HSC daughter cells must then decide whether to return to quiescence and metabolic inactivity or to activate further to proliferate and differentiate and replenish lost blood cells. Although the regulation of HSC activation is not well understood, recent discoveries shed new light on involved mechanisms including asymmetric cell division (ACD). Recent findings HSC metabolism has emerged as a regulator of cell fates. Recent evidence suggests that cellular organelles mediating anabolic and catabolic processes can be asymmetrically inherited during HSC divisions. These include autophagosomes, mitophagosomes, and lysosomes, which regulate HSC quiescence. Their asymmetric inheritance has been linked to future metabolic and translational activity in HSC daughters, showing that ACD can regulate the balance between HSC (in)activity. Summary We discuss recent insights and remaining questions in how HSCs balance activation and quiescence, with a focus on ACD. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.