International Journal of Hematology

DOI: 10.1007/s12185-018-2458-7 Pages: 627-633

Regulation of unfolded protein response in hematopoietic stem cells

1. Lund University, Division of Molecular Medicine and Gene Therapy, Lund Stem Cell Center

Correspondence to:
Kenichi Miharada
Tel: +46 46 222 05 58
Email: Kenichi.Miharada@med.lu.se

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Abstract

Hematopoietic stem cells (HSCs) play a central role in hematopoietic regeneration, which has been demonstrated by thorough studies. In contrast, the cell cycle status and metabolic condition of HSCs define these cells as dormant. Recent studies have also revealed that protein metabolism is quite unique, as dormant HSCs have a lower protein synthesis rate and folding capacity. Under proliferative conditions, upon hematopoietic stress, HSCs need to deal with higher requirements of protein production to achieve fast and effective blood replenishment. In such cases, increased protein synthesis could exceed the capacity of precise protein quality control, leading to the accumulation of unfolded and misfolded proteins. In turn, this triggers endoplasmic reticulum (ER) stress as a part of the unfolded protein response (UPR). Since ER stress is a multi-layered, bidirectional cellular response that contains both positive (survival) and negative (death) reactions, proper management of UPR and ER stress signals is crucial for HSCs and also for maintaining the healthy hematopoietic system. In this review, we introduce the latest findings in this emerging field within hematopoiesis and HSC regulation.

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