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Cited2 is an essential regulator of adult hematopoietic stem cells

Kranc, Kamil R., Schepers, Hein, Rodrigues, Neil, Bamforth, Simon, Villadsen, Ellen, Ferry, Helen, Bouriez-Jones, Tiphaine, Sigvardsson, Mikael, Bhattacharya, Shoumo, Jacobsen, Sten Eirik and Enver, Tariq 2009. Cited2 is an essential regulator of adult hematopoietic stem cells. Cell Stem Cell 5 (6) , pp. 659-665. 10.1016/j.stem.2009.11.001

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Abstract

The regulatory pathways necessary for the maintenance of adult hematopoietic stem cells (HSCs) remain poorly defined. By using loss-of-function approaches, we report a selective and cell-autonomous requirement for the p300/CBP-binding transcriptional coactivator Cited2 in adult HSC maintenance. Conditional deletion of Cited2 in the adult mouse results in loss of HSCs causing multilineage bone marrow failure and increased lethality. In contrast, conditional ablation of Cited2 after lineage specification in lymphoid and myeloid lineages has no impact on the maintenance of these lineages. Additional deletion of Ink4a/Arf (encoding p16Ink4a and p19Arf) or Trp53 (encoding p53, a downstream target of p19Arf) in a Cited2-deficient background restores HSC functionality and rescues mice from bone marrow failure. Furthermore, we show that the critical role of Cited2 in primitive hematopoietic cells is conserved in humans. Taken together, our studies provide genetic evidence that Cited2 selectively maintains adult HSC functions, at least in part, via Ink4a/Arf and Trp53.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH301 Biology
Uncontrolled Keywords: Stemcell
Publisher: Elsevier
ISSN: 1934-5909
Last Modified: 04 Jun 2017 05:21
URI: http://orca-mwe.cf.ac.uk/id/eprint/51135

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