Journal
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
Volume 97, Issue 9, Pages 1291-1294Publisher
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2011.060251
Keywords
Pontin; regulation; hematopoietic stem cell; embryogenesis; adult
Categories
Funding
- FP6 EuroStemCell
- EuroCSC consortia
- MRC Program Grant [93339]
- MRC Strategic Award
- HFSP postdoctoral fellowship
- Jose Carreras Young Investigator Fellowship
- MRC [G0900892, G0701761] Funding Source: UKRI
- Medical Research Council [G0701761, G0900892, G0700711B] Funding Source: researchfish
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Pontin is a highly conserved DNA helicase/ATPase which is a component of several macromolecular complexes with functions that include DNA repair, telomere maintenance and tumor suppression. While Pontin is known to be essential in yeast, fruit flies and frogs, its physiological role in mammalian organisms remains to be determined. We here find that Pontin is highly expressed in embryonic stem cells and hematopoietic tissues. Through germline inactivation of Ruvbl1, the gene encoding Pontin, we found it to be essential for early embryogenesis, as Ruvbl1 null embryos could not be recovered beyond the blastocyst stage where proliferation of the pluripotent inner cell mass was impaired. Conditional ablation of Ruvbl1 in hematopoietic tissues led to bone marrow failure. Competitive repopulation experiments showed that this included the loss of hematopoietic stem cells through apopotosis. Pontin is, therefore, essential for the function of both embryonic pluripotent cells and adult hematopoietic stem cells.
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