Fancd2 and p21 function independently in maintaining the size of hematopoietic stem and progenitor cell pool in mice

Qing Shuo Zhang, Kevin Watanabe-Smith, Kathryn Schubert, Angela Major, Andrea M. Sheehan, Laura Marquez-Loza, Amy E.Hanlon Newell, Eric Benedetti, Eric Joseph, Susan Olson, Markus Grompe

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Fanconi anemia patients suffer from progressive bone marrow failure. An overactive p53 response to DNA damage contributes to the progressive elimination of Fanconi anemia hematopoietic stem and progenitor cells (HSPC), and hence presents a potential target for therapeutic intervention. To investigate whether the cell cycle regulatory protein p21 is the primary mediator of the p53-dependent stem cell loss, p21/Fancd2 double-knockout mice were generated. Surprisingly double mutant mice displayed even more severe loss of HSPCs than Fancd2-/- single mutants. p21 deletion did not rescue the abnormal cell cycle profile and had no impact on the long-term repopulating potential of Fancd2-/- bone marrow cells. Collectively, our data indicate that p21 has an indispensable role in maintaining a normal HSPC pool and suggest that other p53-targeted factors, not p21, mediate the progressive elimination of HSPC in Fanconi anemia.

Original languageEnglish (US)
Pages (from-to)687-692
Number of pages6
JournalStem Cell Research
Volume11
Issue number2
DOIs
StatePublished - Sep 1 2013

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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    Zhang, Q. S., Watanabe-Smith, K., Schubert, K., Major, A., Sheehan, A. M., Marquez-Loza, L., Newell, A. E. H., Benedetti, E., Joseph, E., Olson, S., & Grompe, M. (2013). Fancd2 and p21 function independently in maintaining the size of hematopoietic stem and progenitor cell pool in mice. Stem Cell Research, 11(2), 687-692. https://doi.org/10.1016/j.scr.2013.04.010