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Hormetic endoplasmic reticulum stress in hematopoietic stem cells
1Lindsley F. Kimball Research Institute, New York Blood Center, New York City, New York, USA.
Current Opinion in Hematology
|July 7, 2021
Summary
Endoplasmic reticulum (ER) stress supports hematopoietic stem cell (HSC) regeneration and self-renewal. Understanding these cytoprotective ER stress pathways is key to improving HSC therapies.
Area of Science:
- Hematology
- Cell Biology
- Stress Biology
Background:
- Hematopoietic stem cells (HSCs) exhibit remarkable regenerative capacity throughout life.
- Mechanisms governing HSC regeneration under stress are not fully understood.
- Endoplasmic reticulum (ER) stress is increasingly recognized for its role in HSC maintenance.
Purpose of the Study:
- To review the signaling pathways linking ER stress to cytoprotection in HSCs.
- To summarize the current understanding of ER stress in HSC self-renewal and multipotency.
Main Methods:
- Literature review of recent studies on ER stress and HSCs.
- Analysis of signaling cascades within the unfolded protein response (UPR).
Main Results:
- Persistent, low-dose ER stress, mediated by the UPR, is a characteristic of healthy HSCs.
- This ER stress contributes to HSC cytoprotection, longevity, and adaptation (hormesis).
- Specific upstream activators and downstream transcriptional programs remain to be fully elucidated.
Conclusions:
- Dose-dependent ER stress responses are crucial for HSC maintenance.
- Elucidating ER stress mechanisms may enable ex vivo HSC expansion for transplantation.
- Harnessing ER stress pathways holds potential for advancing cellular therapeutics.
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