No Evidence for Hematopoietic Stem Cell Self-Renewal in-Vivo Following Inflammatory Challenge

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.456-456
• Main Authors: Bogeska, Ruzhica, Kaschutnig, Paul, Paffenholz, Stella V, Knoch, Julia, Mallm, Jan-Philipp, Fawaz, Malak, Buettner, Florian, Walter, Dagmar, Frauhammer, Felix, Holland-Letz, Tim, Asada, Noboru, Mikecin Drazic, Ana-Matea, Buechler-Schaff, Marleen, Correno-Gonzalez, Martha, Ball, Melanie, Staeble, Sina, Gräsel, Julius, Haas, Simon, Lipka, Daniel B., Rippe, Karsten, Brors, Benedikt, Frenette, Paul S., Rieger, Michael A., Essers, Marieke A.G., Milsom, Michael D.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-125744

Elevated levels of inflammation have been previously linked to both inherited and acquired bone marrow failure (BMF) syndromes, as well as to normal aging, suggesting a role in the etiology of these conditions. One potential explanation for this phenomenon is that repeated inflammation can promote the suppression of hematopoietic stem cell (HSC) function.We have previously demonstrated that interferon-α can accelerate HSC attrition by driving HSCs out of quiescence, leading to the development of BMF in a mouse model of Fanconi anemia (Walter et al. Nature, 2015). To more broadly address the impact of repetitive inflammatory challenge on HSC regeneration, we challenged C57BL6 wild type (WT) mice with polyinosinic:polycytidylic acid (pI:C), a TLR3 agonist that mimics viral infection. Injection with 1-3 rounds of pI:C (8 injections per round) in WT mice had no sustained impact on hematopoiesis, since peripheral blood (PB) and bone marrow (BM) counts were within normal ranges at 5 weeks (5wk) post-treatment. However, in vitro analysis of the clonal proliferation potential of 411 individual sorted long-term (LT)-HSCs revealed a 2-fold reduction (p