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Mediators of reprogramming: transcription factors and transitions through mitosis
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Mediators of reprogramming: transcription factors and transitions through mitosis
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Journal Article
Mediators of reprogramming: transcription factors and transitions through mitosis
2008
Overview
Key Points
The genome remains mostly constant during development and ageing.
Cells differ in which part of the genome they express. The gene-expression programme is determined by the presence of transcriptional regulators.
The cloning of various organisms from different cell types shows that the differentiated state and cellular changes that occur during ageing are reversible. This reversion is referred to as reprogramming.
Transcriptional regulators dissociate from the chromatin during cell division. The transcriptional programme, and with it a cellular state, is newly established after every cell division, thereby challenging the old state as well as providing the opportunity to transit to another state.
Exposing a genome to a different set of transcriptional regulators can change its gene-expression programme and with it cellular identity. This can be done by ectopic expression of transcription factors, cell fusion or nuclear transfer.
Transfer of a somatic cell genome into an unfertilized oocyte or a zygote in mitosis allows the derivation of pluripotent embryonic stem-cell lines from the cloned preimplantation stage embryos.
Fusion of a somatic cell with an embryonic stem cell can reprogramme the somatic cell genome to an embryonic state.
The ectopic expression of a combination of embryonic stem-cell transcription factors can reprogramme a somatic cell to an embryonic state.
Animal cloning demonstrates that the genome of a differentiated cell can be reprogrammed to support the development of an entire organism and allow the derivation of pluripotent stem cells. Is there a common mechanism for programming and reprogramming developmental states? And what factors are required?
It is thought that most cell types of the human body share the same genetic information as that contained in the zygote from which they originate. Consistent with this view, animal cloning studies demonstrated that the intact genome of a differentiated cell can be reprogrammed to support the development of an entire organism and allow the production of pluripotent stem cells. Recent progress in reprogramming research now points to an important role for transcription factors in the establishment and the maintenance of cellular phenotypes, and to cell division as a mediator of transitions between different states of gene expression.
Publisher
Nature Publishing Group UK,Nature Publishing Group
