Id1 restrains p21 expression to control endothelial progenitor cell formation

Alessia Ciarrocchi, Vladimir Jankovic, Yuval Shaked, Daniel J. Nolan, Vivek Mittal, Robert S. Kerbel, Stephen D. Nimer, Robert Benezra

Research output: Contribution to journalArticle


Loss of Id1 in the bone marrow (BM) severely impairs tumor angiogenesis resulting in significant inhibition of tumor growth. This phenotype has been associated with the absence of circulating endothelial progenitor cells (EPCs) in the peripheral of Id1 mutant mice. However, the manner in which Id1 loss in the BM controls EPC generation or mobilization is largely unknown. Using genetically modified mouse models we demonstrate here that the generation of EPCs in the BM depends the ability of Id1 to restrain the expression of its target gene p21. Through a series of cellular and functional studies we that the increased myeloid commitment of BM stem cells and the absence of EPCs in Id1 knockout mice are associated elevated p21 expression. Genetic ablation of p21 rescues the EPC population in the Id1 null animals, re-establishing functional BM-derived angiogenesis and restoring normal tumor growth. These results demonstrate that the restraint of p21 expression by Id1 is one key element of its activity in facilitating the generation of EPCs in the BM and highlight the critical role these play in tumor angiogenesis.

Original languageEnglish
Article numbere1338
JournalPLoS One
Issue number12
Publication statusPublished - Dec 19 2007


ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Ciarrocchi, A., Jankovic, V., Shaked, Y., Nolan, D. J., Mittal, V., Kerbel, R. S., Nimer, S. D., & Benezra, R. (2007). Id1 restrains p21 expression to control endothelial progenitor cell formation. PLoS One, 2(12), [e1338].