Datasets

Title	Human Hematopoietic Stem Cell Vulnerability to Ferroptosis [Ribosome profiling]
Organism
Number of Samples	6
Release Date	2022/12/16 00:00
Sequencing Types
Protocol Details

Title
Authors	Zhao J, Jia Y, Mahmut D, Deik AA, Jeanfavre S, Clish CB, Sankaran VG
Journal	Cell
Publication Date	2023 Feb 16
Abstract	Hematopoietic stem cells (HSCs) have a number of unique physiologic adaptations that enable lifelong maintenance of blood cell production, including a highly regulated rate of protein synthesis. Yet, the precise vulnerabilities that arise from such adaptations have not been fully characterized. Here, inspired by a bone marrow failure disorder due to the loss of the histone deubiquitinase MYSM1, characterized by selectively disadvantaged HSCs, we show how reduced protein synthesis in HSCs results in increased ferroptosis. HSC maintenance can be fully rescued by blocking ferroptosis, despite no alteration in protein synthesis rates. Importantly, this selective vulnerability to ferroptosis not only underlies HSC loss in MYSM1 deficiency but also characterizes a broader liability of human HSCs. Increasing protein synthesis rates via MYSM1 overexpression makes HSCs less susceptible to ferroptosis, more broadly illustrating the selective vulnerabilities that arise in somatic stem cell populations as a result of physiologic adaptations. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.
PMC	PMC9978939
PMID	36803603
DOI

0.0 et al. 2023 (PRJNA913269)