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Regulation of unfolded protein response in hematopoietic stem cells

Sigurdsson, Valgardur LU and Miharada, Kenichi LU (2018) In International Journal of Hematology
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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Bile acid, ER stress, Hematopoietic stem cell, Proteostasis, Unfolded protein response
in
International Journal of Hematology
pages
7 pages
publisher
Carden Jennings Publishing Co., Ltd.
external identifiers
  • scopus:85046404673
ISSN
0925-5710
DOI
10.1007/s12185-018-2458-7
language
English
LU publication?
yes
id
3d88fe99-14dd-4d71-bb84-4e161d561fe9
date added to LUP
2018-05-15 12:22:51
date last changed
2018-06-03 05:06:38
@article{3d88fe99-14dd-4d71-bb84-4e161d561fe9,
  abstract     = {<p>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.</p>},
  author       = {Sigurdsson, Valgardur and Miharada, Kenichi},
  issn         = {0925-5710},
  keyword      = {Bile acid,ER stress,Hematopoietic stem cell,Proteostasis,Unfolded protein response},
  language     = {eng},
  month        = {05},
  pages        = {7},
  publisher    = {Carden Jennings Publishing Co., Ltd.},
  series       = {International Journal of Hematology},
  title        = {Regulation of unfolded protein response in hematopoietic stem cells},
  url          = {http://dx.doi.org/10.1007/s12185-018-2458-7},
  year         = {2018},
}