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Bile Acids Protect Expanding Hematopoietic Stem Cells from Unfolded Protein Stress in Fetal Liver.

Sigurdsson, Valgardur LU ; Takei, Hajime; Soboleva, Svetlana LU ; Radulovic, Visnja LU ; Galeev, Roman LU ; Siva, Kavitha LU ; Leeb-Lundberg, Fredrik LU ; Iida, Takashi; Nittono, Hiroshi and Miharada, Kenichi LU (2016) In Cell Stem Cell 18(4). p.32-522
Abstract
During development, hematopoietic stem cells (HSCs) undergo a rapid expansion in the fetal liver (FL) before settling in the adult bone marrow. We recently reported that proliferating adult HSCs are vulnerable to ER stress caused by accumulation of mis-folded proteins. Here, we find that FL-HSCs, despite an increased protein synthesis rate and a requirement for protein folding, do not upregulate ER chaperones. Instead, bile acids (BAs), secreted from maternal and fetal liver, coordinate to serve as chemical chaperones. Taurocholic acid, the major BA in FL, supports growth of HSCs in vitro by inhibiting protein aggregation. In vivo, reducing BA levels leads to ER stress elevation and accumulation of aggregated proteins and significantly... (More)
During development, hematopoietic stem cells (HSCs) undergo a rapid expansion in the fetal liver (FL) before settling in the adult bone marrow. We recently reported that proliferating adult HSCs are vulnerable to ER stress caused by accumulation of mis-folded proteins. Here, we find that FL-HSCs, despite an increased protein synthesis rate and a requirement for protein folding, do not upregulate ER chaperones. Instead, bile acids (BAs), secreted from maternal and fetal liver, coordinate to serve as chemical chaperones. Taurocholic acid, the major BA in FL, supports growth of HSCs in vitro by inhibiting protein aggregation. In vivo, reducing BA levels leads to ER stress elevation and accumulation of aggregated proteins and significantly decreases the number of FL-HSCs. Taken together, these findings reveal that BA alleviation of ER stress is a mechanism required for HSC expansion during fetal hematopoiesis. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Cell Stem Cell
volume
18
issue
4
pages
32 - 522
publisher
Cell Press
external identifiers
  • pmid:26831518
  • wos:000373722100015
  • scopus:84962097666
ISSN
1934-5909
DOI
10.1016/j.stem.2016.01.002
language
English
LU publication?
yes
id
1ece2107-a8be-47d3-afdc-718f85d6dcb4 (old id 8830041)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26831518?dopt=Abstract
date added to LUP
2016-03-01 11:50:28
date last changed
2017-10-22 04:54:30
@article{1ece2107-a8be-47d3-afdc-718f85d6dcb4,
  abstract     = {During development, hematopoietic stem cells (HSCs) undergo a rapid expansion in the fetal liver (FL) before settling in the adult bone marrow. We recently reported that proliferating adult HSCs are vulnerable to ER stress caused by accumulation of mis-folded proteins. Here, we find that FL-HSCs, despite an increased protein synthesis rate and a requirement for protein folding, do not upregulate ER chaperones. Instead, bile acids (BAs), secreted from maternal and fetal liver, coordinate to serve as chemical chaperones. Taurocholic acid, the major BA in FL, supports growth of HSCs in vitro by inhibiting protein aggregation. In vivo, reducing BA levels leads to ER stress elevation and accumulation of aggregated proteins and significantly decreases the number of FL-HSCs. Taken together, these findings reveal that BA alleviation of ER stress is a mechanism required for HSC expansion during fetal hematopoiesis.},
  author       = {Sigurdsson, Valgardur and Takei, Hajime and Soboleva, Svetlana and Radulovic, Visnja and Galeev, Roman and Siva, Kavitha and Leeb-Lundberg, Fredrik and Iida, Takashi and Nittono, Hiroshi and Miharada, Kenichi},
  issn         = {1934-5909},
  language     = {eng},
  number       = {4},
  pages        = {32--522},
  publisher    = {Cell Press},
  series       = {Cell Stem Cell},
  title        = {Bile Acids Protect Expanding Hematopoietic Stem Cells from Unfolded Protein Stress in Fetal Liver.},
  url          = {http://dx.doi.org/10.1016/j.stem.2016.01.002},
  volume       = {18},
  year         = {2016},
}