The Paf oncogene is essential for hematopoietic stem cell function and development

Yacine M. Amrani, Jonathan Gill, Armine Matevossian, Eric S. Alonzo, Chingwen Yang, Jae Hung Shieh, Malcolm A. Moore, Christopher Y. Park, Derek B. Sant'Angelo, Lisa K. Denzin

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19 Scopus citations

Abstract

Hematopoietic stem cells (HSCs) self-renew to maintain the lifelong production of all blood populations. Here, we show that the proliferating cell nuclear antigen-associated factor (Paf) is highly expressed in cycling bone marrow HSCs and plays a critical role in hematopoiesis. Mice lacking Paf exhibited reduced bone marrow cellularity; reduced numbers of HSCs and committed progenitors; and leukopenia. These phenotypes are caused by a cellintrinsic blockage in the development of long-term (LT)-HSCs into multipotent progenitors and preferential loss of lymphoid progenitors caused by markedly increased p53-mediated apoptosis. In addition, LT-HSCs from Paf-/- mice had increased levels of reactive oxygen species (ROS), failed to maintain quiescence, and were unable to support LT hematopoiesis. The loss of lymphoid progenitors was likely due the increased levels of ROS in LT-HSCs caused by treatment of Paf-/- mice with the anti-oxidant N-acetylcysteine restored lymphoid progenitor numbers to that of Paf+/+ mice. Collectively, our studies identify Paf as a novel and essential regulator of early hematopoiesis. 2011 Amrani et al.

Original languageEnglish (US)
Pages (from-to)1757-1765
Number of pages9
JournalJournal of Experimental Medicine
Volume208
Issue number9
DOIs
StatePublished - Aug 29 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Amrani, Y. M., Gill, J., Matevossian, A., Alonzo, E. S., Yang, C., Shieh, J. H., Moore, M. A., Park, C. Y., Sant'Angelo, D. B., & Denzin, L. K. (2011). The Paf oncogene is essential for hematopoietic stem cell function and development. Journal of Experimental Medicine, 208(9), 1757-1765. https://doi.org/10.1084/jem.20102170