Journal
CELL STEM CELL
Volume 18, Issue 4, Pages 522-532Publisher
CELL PRESS
DOI: 10.1016/j.stem.2016.01.002
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Funding
- Swedish Research Council
- Swedish Cancer Society
- Ake-Wibergs foundation
- Crafoord foundation
- StemTherapy program at Lund University
- Center of Excellence grant in life sciences from the Swedish Foundation for Strategic Research
- Grants-in-Aid for Scientific Research [15K01809] Funding Source: KAKEN
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Duringdevelopment, hematopoietic stemcells (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.
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