A dynamic model of keratinocyte stem cell renewal and differentiation: role of the p21WAF1/Cip1 and Notch1 signaling pathways.
We present here a dynamic model of functional equilibrium between keratinocyte stem cells, transit amplifying populations and cells that are reversibly versus irreversibly committed to differentiation. According to this model, the size of keratinocyte stem cell populations can be controlled at multiple levels, including relative late steps in the sequence of events leading to terminal differentiation and by the influences of a heterogeneous extra-cellular environment. We discuss how work in our laboratory, on the interconnection between the cyclin/CDK inhibitor p21WAF1/Cip1 and the Notch1 signaling pathways, provides strong support to this dynamic model of stem cell versus committed and/or differentiated keratinocyte populations.
Okuyama
Ryuhei
R
Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
LeFort
Karine
K
Dotto
G Paolo
GP
D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology*; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors