Hochedlinger K, Yamada Y, Beard C, Jaenisch R.
Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues.
Cell. 2005 May 6;121(3):465-77.
PubMed.
The findings of Hochedlinger et al. provide an important advance in our understanding of the contribution of the POU-domain transcription factor, Oct-4, to stem cells and their differentiation in mammals. Their data strongly suggest that ectopic expression of Oct-4 in adult mice, using a doxycycline-dependent expression system, results in dysplastic growth in epithelial tissues that is dependent on continuous Oct-4 expression. Thus, the reversible expansion of progenitor cells by Oct-4 induction might have great potential for disease prevention or treatment. For example, in neurodegenerative disorders such as Alzheimer disease or Parkinson disease, it has been reported that there is limited neural progenitor cells in the diseased brains. If the similar approach would be taken, it might increase progenitor cells in the diseased brains; then, reduction of Oct-4 expression would be assumed to enhance the differentiation of these progenitor cells to new neurons. However, there is one major technical issue—entry of doxycycline into the brain. This drug does not readily pass the blood-brain barrier.
The design of the study, which involved using a doxycycline-dependent expression system, was excellent and revealed the complexity of differential expression during embryonic and adult periods. The availability of this type of transgenic mice, using a doxycycline-dependent expression system under control of a specific neuronal promoter, would be very valuable to the biomedical research community and help to determine the role of neurogenesis in various age-related diseases.
Comments
Roskamp Institute
The findings of Hochedlinger et al. provide an important advance in our understanding of the contribution of the POU-domain transcription factor, Oct-4, to stem cells and their differentiation in mammals. Their data strongly suggest that ectopic expression of Oct-4 in adult mice, using a doxycycline-dependent expression system, results in dysplastic growth in epithelial tissues that is dependent on continuous Oct-4 expression. Thus, the reversible expansion of progenitor cells by Oct-4 induction might have great potential for disease prevention or treatment. For example, in neurodegenerative disorders such as Alzheimer disease or Parkinson disease, it has been reported that there is limited neural progenitor cells in the diseased brains. If the similar approach would be taken, it might increase progenitor cells in the diseased brains; then, reduction of Oct-4 expression would be assumed to enhance the differentiation of these progenitor cells to new neurons. However, there is one major technical issue—entry of doxycycline into the brain. This drug does not readily pass the blood-brain barrier.
The design of the study, which involved using a doxycycline-dependent expression system, was excellent and revealed the complexity of differential expression during embryonic and adult periods. The availability of this type of transgenic mice, using a doxycycline-dependent expression system under control of a specific neuronal promoter, would be very valuable to the biomedical research community and help to determine the role of neurogenesis in various age-related diseases.
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