Guarnerio, JleniaColtella, NadiaAla, UgoTonon, GiovanniPandolfi, Pier PaoloBernardi, Rosa2014-07-072014Guarnerio, Jlenia, Nadia Coltella, Ugo Ala, Giovanni Tonon, Pier Paolo Pandolfi, and Rosa Bernardi. 2014. “Bone Marrow Endosteal Mesenchymal Progenitors Depend on HIF Factors for Maintenance and Regulation of Hematopoiesis.” Stem Cell Reports 2 (6): 794-809. doi:10.1016/j.stemcr.2014.04.002. http://dx.doi.org/10.1016/j.stemcr.2014.04.002.2213-6711http://nrs.harvard.edu/urn-3:HUL.InstRepos:12406663Summary Maintenance and differentiation of hematopoietic stem cells (HSCs) is regulated through cell-autonomous and non-cell-autonomous mechanisms within specialized bone marrow microenvironments. Recent evidence demonstrates that signaling by HIF-1α contributes to cell-autonomous regulation of HSC maintenance. By investigating the role of HIF factors in bone marrow mesenchymal progenitors, we found that murine endosteal mesenchymal progenitors express high levels of HIF-1α and HIF-2α and proliferate preferentially in hypoxic conditions ex vivo. Inactivation of either HIF-1α or HIF-2α dramatically affects their phenotype, propagation, and differentiation. Also, downregulation of HIF factors provokes an increase in interferon-responsive genes and triggers expansion and differentiation of hematopoietic progenitors by a STAT1-mediated mechanism. Interestingly, in conditions of demand-driven hematopoiesis HIF factors are specifically downregulated in mesenchymal progenitors in vivo. In conclusion, our findings indicate that HIF factors also regulate hematopoiesis non-cell-autonomously by preventing activation of a latent program in mesenchymal progenitors that promotes hematopoiesis.en-USJournal Article2014-07-0710.1016/j.stemcr.2014.04.002