Project description:Regulation of transit amplifying cell formation from self-renewing stem cell is fundamental process for cell replacement in a controlled way. Here we analyse the properties of a population of mesenchymal TACs in the continuously growing mouse incisor to identify key components of the molecular regulation that drives proliferation. We show that the polycomb repressive complex 1 acts as a global regulator of the TAC phenotype by its direct action on the expression of key cell cycle regulatory genes and also by regulating Wnt/b-catenin signalling activity. We also identify an essential requirement for TACs in maintaining the mesenchymal stem cells, indicative of a positive feedback mechanism. Analysing the properties of mesenchymal transit amplifying cells population and identifing key components of the molecular regulation that drives proliferation.
Project description:Regulation of transit amplifying cell formation from self-renewing stem cell is fundamental process for cell replacement in a controlled way. Here we analyse the properties of a population of mesenchymal TACs in the continuously growing mouse incisor to identify key components of the molecular regulation that drives proliferation. Using gene microarray profiling, we show that the polycomb repressive complex 1 acts as a global regulator of the TAC phenotype by its direct action on the expression of key cell cycle regulatory genes and also by regulating Wnt/b-catenin signalling activity. Analysing the properties of mesenchymal transit amplifying cells population and identifing key components of the molecular regulation that drives proliferation.
Project description:Regulation of transit amplifying cell formation from self-renewing stem cell is fundamental process for cell replacement in a controlled way. Here we analyse the properties of a population of mesenchymal TACs in the continuously growing mouse incisor to identify key components of the molecular regulation that drives proliferation. We show that the polycomb repressive complex 1 acts as a global regulator of the TAC phenotype by its direct action on the expression of key cell cycle regulatory genes and also by regulating Wnt/b-catenin signalling activity. We also identify an essential requirement for TACs in maintaining the mesenchymal stem cells, indicative of a positive feedback mechanism. Analysing the properties of mesenchymal transit amplifying cells population and identifing key components of the molecular regulation that drives proliferation.
Project description:Regulation of mesenchymal stem to transit amplifying cell transition in the continuously growing mouse incisor [Microarray Expression]
Project description:In adult tissues and organs with high turnover rates, the generation of transit-amplifying cell (TAC) populations from self-renewing stem cells drives cell replacement. The role of stem cells is to provide a renewable source of cells that give rise to TACs to provide the cell numbers that are necessary for cell differentiation. Regulation of the formation of TACs is thus fundamental to controlling cell replacement. Here, we analyze the properties of a population of mesenchymal TACs in the continuously growing mouse incisor to identify key components of the molecular regulation that drives proliferation. We show that the polycomb repressive complex 1 acts as a global regulator of the TAC phenotype by its direct action on the expression of key cell-cycle regulatory genes and by regulating Wnt/β-catenin-signaling activity. We also identify an essential requirement for TACs in maintaining mesenchymal stem cells, which is indicative of a positive feedback mechanism.
Project description:To explore which signaling pathways are of importance in maintenance of human epidermal keratinocytes we have established a protocol which allows single cell expression profiling. The protocol was applied to cultured human epidermal keratinocytes, and single cell cDNA libraries from stem and transit amplifying cells were identified based on the expression of known SC markers, MCSP and Dll1. We used microarrays to obtain expression profiles from single cells and identify common denominators that could be important for maintenance and signalling in epidermal stem cells. Keywords: Timecourse