Cited2 Is an Essential Regulator of Adult Hematopoietic Stem Cells

Kamil R Kranc, Hein Schepers, Neil P Rodrigues, Simon Bamforth, Ellen Villadsen, Helen Ferry, Tiphaine Bouriez-Jones, Mikael Sigvardsson, Shoumo Bhattacharya, Sten Eirik Jacobsen, Tariq Enver

Research output: Contribution to journalArticlepeer-review

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 p16(Ink4a) and p19(Arf)) or Trp53 (encoding p53, a downstream target of p19(Arf)) 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.
Original languageEnglish
Pages (from-to)659-665
Number of pages7
JournalCell Stem Cell
Volume5
Issue number6
DOIs
Publication statusPublished - 4 Dec 2009

Keywords

  • ADP-Ribosylation Factors
  • Adult Stem Cells
  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Cyclin-Dependent Kinase Inhibitor p16
  • Hematopoietic Stem Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Small Interfering
  • Repressor Proteins
  • Trans-Activators
  • Transcriptional Activation
  • Tumor Suppressor Protein p53
  • p300-CBP Transcription Factors

Fingerprint

Dive into the research topics of 'Cited2 Is an Essential Regulator of Adult Hematopoietic Stem Cells'. Together they form a unique fingerprint.

Cite this