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Endoplasmic reticulum stress regulation in hematopoietic stem cells

Miharada, Kenichi LU (2016) In [Rinsho ketsueki] The Japanese journal of clinical hematology 57(8). p.1052-1058
Abstract

Adult hematopoietic stem cells (HSCs) reside in bone marrow and are maintained in a dormant state within a special microenvironment, their so-called "niche". Detaching from the niche induces cell cycle progression, resulting in a reduction of the reconstitution capacity of HSCs. In contrast, fetal liver HSCs actively divide without losing their stem cell potentials. Thus, it has been unclear what types of cellular responses and metabolic changes occur in growing HSCs. We previously discovered that HSCs express relatively low levels of endoplasmic reticulum (ER) chaperone proteins governing protein folding, making HSCs vulnerable to an elevation of stress signals caused by accumulation of un-/misfolded proteins (ER stress) upon in vitro... (More)

Adult hematopoietic stem cells (HSCs) reside in bone marrow and are maintained in a dormant state within a special microenvironment, their so-called "niche". Detaching from the niche induces cell cycle progression, resulting in a reduction of the reconstitution capacity of HSCs. In contrast, fetal liver HSCs actively divide without losing their stem cell potentials. Thus, it has been unclear what types of cellular responses and metabolic changes occur in growing HSCs. We previously discovered that HSCs express relatively low levels of endoplasmic reticulum (ER) chaperone proteins governing protein folding, making HSCs vulnerable to an elevation of stress signals caused by accumulation of un-/misfolded proteins (ER stress) upon in vitro culture. Interestingly, fetal liver HSCs do not show ER stress elevation despite unchanged levels of chaperone proteins. Our latest studies utilizing multiple mouse models revealed that in the fetal liver bile acids as chemical chaperones play a key role supporting the protein folding which results in the suppression of ER stress induction. These findings highlight the importance of ER stress regulations in hematopoiesis.

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organization
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type
Contribution to journal
publication status
published
subject
in
[Rinsho ketsueki] The Japanese journal of clinical hematology
volume
57
issue
8
pages
7 pages
publisher
Nihon Rinsho Ketsueki Gakkai/Japan Society of Clinical Hematology
external identifiers
  • scopus:85011982635
ISSN
0485-1439
DOI
10.11406/rinketsu.57.1052
language
English
LU publication?
yes
id
d2cea125-beee-4e9c-8a45-fc667e6e8abf
date added to LUP
2017-03-03 13:26:28
date last changed
2017-03-03 13:26:28
@article{d2cea125-beee-4e9c-8a45-fc667e6e8abf,
  abstract     = {<p>Adult hematopoietic stem cells (HSCs) reside in bone marrow and are maintained in a dormant state within a special microenvironment, their so-called "niche". Detaching from the niche induces cell cycle progression, resulting in a reduction of the reconstitution capacity of HSCs. In contrast, fetal liver HSCs actively divide without losing their stem cell potentials. Thus, it has been unclear what types of cellular responses and metabolic changes occur in growing HSCs. We previously discovered that HSCs express relatively low levels of endoplasmic reticulum (ER) chaperone proteins governing protein folding, making HSCs vulnerable to an elevation of stress signals caused by accumulation of un-/misfolded proteins (ER stress) upon in vitro culture. Interestingly, fetal liver HSCs do not show ER stress elevation despite unchanged levels of chaperone proteins. Our latest studies utilizing multiple mouse models revealed that in the fetal liver bile acids as chemical chaperones play a key role supporting the protein folding which results in the suppression of ER stress induction. These findings highlight the importance of ER stress regulations in hematopoiesis. </p>},
  author       = {Miharada, Kenichi},
  issn         = {0485-1439},
  language     = {eng},
  number       = {8},
  pages        = {1052--1058},
  publisher    = {Nihon Rinsho Ketsueki Gakkai/Japan Society of Clinical Hematology},
  series       = {[Rinsho ketsueki] The Japanese journal of clinical hematology},
  title        = {Endoplasmic reticulum stress regulation in hematopoietic stem cells},
  url          = {http://dx.doi.org/10.11406/rinketsu.57.1052},
  volume       = {57},
  year         = {2016},
}