Next Article in Journal
Computational Prediction of RNA-Binding Proteins and Binding Sites
Next Article in Special Issue
Dermal Contributions to Human Interfollicular Epidermal Architecture and Self-Renewal
Previous Article in Journal
Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells
Previous Article in Special Issue
Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(11), 26291-26302;

Notch Cooperates with Survivin to Maintain Stemness and to Stimulate Proliferation in Human Keratinocytes during Ageing

Laboratory of Cutaneous Biology, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, via del Pozzo 71, Modena 41121, Italy
LVMH Recherche, 185 Avenue de Verdun, Saint Jean de Braye 45800, France
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Miroslav Blumenberg
Received: 17 September 2015 / Revised: 9 October 2015 / Accepted: 22 October 2015 / Published: 3 November 2015
(This article belongs to the Special Issue Molecular Research of Epidermal Stem Cells 2015)
PDF [4300 KB, uploaded 3 November 2015]


The Notch signaling pathway orchestrates cell fate by either inducing cell differentiation or maintaining cells in an undifferentiated state. This study aims to evaluate Notch expression and function in normal human keratinocytes. Notch1 is expressed in all epidermal layers, though to a different degree of intensity, with a dramatic decrease during ageing. Notch1 intracellular domain (N1ICD) levels are decreased during transit from keratinocyte stem cells (KSC) to transit amplifying (TA) cells, mimicking survivin expression in samples from donors of all ages. Calcium markedly reduces N1ICD levels in keratinocytes. N1ICD overexpression induces the up-regulation of survivin and the down-regulation of keratin 10 and involucrin, while increasing the S phase of the cell cycle. On the other hand, Notch1 inhibition (DAPT) dose-dependently decreases survivin, stimulates differentiation, and reduces keratinocyte proliferation in samples from donors of all ages. Silencing Notch downgrades survivin and increases keratin 10. In addition, Notch1 inhibition decreases survivin levels and proliferation both in KSC and TA cells. Finally, while survivin overexpression decreases keratinocyte differentiation and increases N1ICD expression both in KSC and TA cells, silencing survivin results in N1ICD down-regulation and an increase in differentiation markers. These results suggest that the Notch1/survivin crosstalk contributes to the maintenance of stemness in human keratinocytes. View Full-Text
Keywords: Notch1; survivin; keratinocytes; stem cells Notch1; survivin; keratinocytes; stem cells

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Palazzo, E.; Morandi, P.; Lotti, R.; Saltari, A.; Truzzi, F.; Schnebert, S.; Dumas, M.; Marconi, A.; Pincelli, C. Notch Cooperates with Survivin to Maintain Stemness and to Stimulate Proliferation in Human Keratinocytes during Ageing. Int. J. Mol. Sci. 2015, 16, 26291-26302.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top