Pontin is essential for murine hematopoietic stem cell survival

Oxana Bereshchenko, Elena Mancini, Luisa Luciani, Adriana Gambardella, Carlo Riccardi, Claus Nerlov

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)1291-1294
Number of pages4
JournalHaematologica
Volume97
Issue number9
DOIs
Publication statusPublished - 30 Sep 2012

Keywords

  • Pontin
  • regulation
  • hematopoietic stem cell
  • embryogenesis
  • adult

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