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

Summary, in English

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: Valgardur Sigurdsson; Hajime Takei; Svetlana Soboleva; Visnja Radulovic; Roman Galeev; Kavitha Siva; Fredrik Leeb-Lundberg; Takashi Iida; Hiroshi Nittono; Kenichi Miharada
• Department/s: Division of Molecular Medicine and Gene Therapy; Stem Cell Metabolism; Drug Target Discovery; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation; StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
• Publishing year: 2016
• Language: English
• Pages: 32-522
• Publication/Series: Cell Stem Cell
• Volume: 18
• Issue: 4
• Links: http://www.ncbi.nlm.nih.gov/pubmed/26831518?dopt=Abstract; http://dx.doi.org/10.1016/j.stem.2016.01.002
• Document type: Journal article
• Publisher: Cell Press
• Topic: Cell and Molecular Biology
• Status: Published
• Research group: Stem Cell Metabolism; Drug Target Discovery
• ISBN/ISSN/Other: ISSN: 1934-5909