The Paf oncogene is essential for hematopoietic stem cell function and development Journal Article
| Authors: | 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. |
| Article Title: | The Paf oncogene is essential for hematopoietic stem cell function and development |
| 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. |
| Keywords: | controlled study; nonhuman; cell proliferation; animal cell; mouse; phenotype; gene targeting; apoptosis; bone marrow; leukopenia; animal experiment; protein p53; monoclonal antibody; oncogene; blood; messenger rna; western blotting; reactive oxygen metabolite; hematopoiesis; real time polymerase chain reaction; antioxidant; hematopoietic stem cell; bone marrow transplantation; lymphoid progenitor cell; fluorescence activated cell sorting; complementary dna; acetylcysteine; paf oncogene |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 208 |
| Issue: | 9 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2011-08-29 |
| Start Page: | 1757 |
| End Page: | 1765 |
| Language: | English |
| DOI: | 10.1084/jem.20102170 |
| PUBMED: | 21844206 |
| PROVIDER: | scopus |
| PMCID: | PMC3171089 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 9 December 2011" - "CODEN: JEMEA" - "Source: Scopus" |
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