BMC/GPMLS Seminar Wednesday, 1st July at 11:00 in Room 343, Læknagarður

Presenter: Dr. Valgarður Sigurðsson, with a post-doc position in the group of Kenichi Miharada : Protein quality control and metabolic regulation in stem cells

Division of Molecular Medicine and Gene Therapy, Lund Strategic Center for Stem Cell Biology, Lund University, Lund, Sweden.

Title: Bile acids protect expanding haematopoietic cells in the fetal liver

Abstract: Hematopoietic stem cells (HSCs) are expanded in fetal liver (FL), while they are maintained in dormant state in adult bone marrow (BM). Mechanisms enabling this are not fully uncovered. This is especially interesting since HSCs are known to be vulnerable to accumulation of un-/mis-folded proteins and subsequent activation of endoplasmic reticulum (ER) stress responses. We set out to discover how expanding HSCs deal with the higher requirement of protein folding in FL. Our data suggests that bile acids (BA) act as natural chaperones to eliminate ER stress and to support expansion of HSCs in FL. By decreasing BA production using a pseudo-negative feedback signal through FxR or deletion of Cyp27a1 from mother and fetus we see a drastic decrease in the number of HSCs. This decrease was due to ER stress and the effect could be rescued by either supplementing BA or inhibiting ER stress induced apoptosis. The work proposes that BAs have a very novel role in the FL, heavily contributing to HSC expansion.