These authors contributed equally to this work
Hedgehog controls neural stem cells through p53-independent regulation of Nanog
Article first published online: 25 JUN 2010
Copyright © 2010 European Molecular Biology Organization
The EMBO Journal
Volume 29, Issue 15, pages 2646–2658, August 4, 2010
How to Cite
Po, A., Ferretti, E., Miele, E., De Smaele, E., Paganelli, A., Canettieri, G., Coni, S., Di Marcotullio, L., Biffoni, M., Massimi, L., Di Rocco, C., Screpanti, I. and Gulino, A. (2010), Hedgehog controls neural stem cells through p53-independent regulation of Nanog. The EMBO Journal, 29: 2646–2658. doi: 10.1038/emboj.2010.131
There is a Have you seen ...? (August 2010) associated with this Article.
- Issue published online: 4 AUG 2010
- Article first published online: 25 JUN 2010
- Manuscript Accepted: 20 MAY 2010
- Manuscript Received: 3 MAR 2010
- neural stem cells
Hedgehog (Hh) pathway has a pivotal function in development and tumorigenesis, processes sustained by stem cells (SCs). The transcription factor Nanog controls stemness acting as a key determinant of both embryonic SC self-renewal and differentiated somatic cells reprogramming to pluripotency, in concert with the loss of the oncosuppressor p53. How Nanog is regulated by microenvironmental signals in postnatal SC niches has been poorly investigated. Here, we show that Nanog is highly expressed in SCs from postnatal cerebellum and medulloblastoma, and acts as a critical mediator of Hh-driven self-renewal. Indeed, the downstream effectors of Hh activity, Gli1 and Gli2, bind to Nanog-specific cis-regulatory sequences both in mouse and human SCs. Loss of p53, a key event promoting cell stemness, activates Hh signalling, thereby contributing to Nanog upregulation. Conversely, Hh downregulates p53 but does not require p53 to control Nanog. Our data reveal a mechanism for the function of Hh in the control of stemness that represents a crucial component of an integrated circuitry determining cell fate decision and involved in the maintenance of cancer SCs.