HEMATOPOIESIS: Edited by Hal E. Broxmeyer and Maegan L. CapitanoHematopoietic stem cell regulation by the proteostasis networkChua, Bernadette A.; Signer, Robert A.J.Author Information Department of Medicine, Division of Regenerative Medicine, Moores Cancer Center, University of California San Diego, La Jolla, California, USA Correspondence to Robert A.J. Signer, PhD, Department of Medicine, Division of Regenerative Medicine, Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093, USA. Tel: +858 534 0732; e-mail: firstname.lastname@example.org, @SignerLab Current Opinion in Hematology: July 2020 - Volume 27 - Issue 4 - p 254-263 doi: 10.1097/MOH.0000000000000591 Buy Metrics Abstract Purpose of review Protein homeostasis (proteostasis) is maintained by an integrated network of physiological mechanisms and stress response pathways that regulate the content and quality of the proteome. Maintenance of cellular proteostasis is key to ensuring normal development, resistance to environmental stress, coping with infection, and promoting healthy aging and lifespan. Recent studies have revealed that several proteostasis mechanisms can function in a cell-type-specific manner within hematopoietic stem cells (HSCs). Here, we review recent studies demonstrating that the proteostasis network functions uniquely in HSCs to promote their maintenance and regenerative function. Recent findings The proteostasis network is regulated differently in HSCs as compared with restricted hematopoietic progenitors. Disruptions in proteostasis are particularly detrimental to HSC maintenance and function. These findings suggest that multiple aspects of cellular physiology are uniquely regulated in HSCs to maintain proteostasis, and that precise control of proteostasis is particularly important to support life-long HSC maintenance and regenerative function. Summary The proteostasis network is uniquely configured within HSCs to promote their longevity and hematopoietic function. Future work uncovering cell-type-specific differences in proteostasis network configuration, integration, and function will be essential for understanding how HSCs function during homeostasis, in response to stress, and in disease. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.