Bile Acids Protect Expanding Hematopoietic Stem Cells from Unfolded Protein Stress in Fetal Liver.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8830041
- author
- 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
- organization
- publishing date
- 2016
- 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
- pmid:26831518
- 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
- 2016-04-04 08:33:30
- date last changed
- 2022-03-23 02:31:30
@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}}, doi = {{10.1016/j.stem.2016.01.002}}, volume = {{18}}, year = {{2016}}, }