Bone marrow endosteal mesenchymal progenitors depend on HIF factors for maintenance and regulation of hematopoiesis

Jlenia Guarnerio, Nadia Coltella, Ugo Ala, Giovanni Tonon, Pier Paolo Pandolfi, Rosa Bernardi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)794-809
Number of pages16
JournalStem Cell Reports
Volume2
Issue number6
DOIs
Publication statusPublished - Jun 3 2014

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Developmental Biology
  • Genetics
  • Medicine(all)

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