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Football Manager 2011. DUTCH.LTC Repackl




The ability to generate a large population of differentiated stem cells is an important milestone in stem cell-based therapies, and it is likely to be crucial for clinical success in regenerative medicine. Two major methods are currently used for generating stem cells: embryogenesis and somatic cell reprogramming. Embryogenesis is a complicated process that leads to the development of all the specialized cell types required for a mature, healthy human. In comparison, somatic cell reprogramming is much more efficient and has the advantage of not requiring the blastocyst stage of development to obtain a stem cell population. Somatic cell reprogramming involves the insertion of an exogenous gene, called the “transcription factor”, into a cell's genome and is achieved by expressing a transcription factor (TF) in a cell that is not normally competent to express that TF. Pou5f1 (Oct4) is a transcription factor found to be necessary for the self-renewal of embryonic stem (ES) cells. Its role in the self-renewal of adult stem cells (ASCs) is not well understood. The ectopic expression of Oct4 is sufficient to reprogram adult mouse fibroblasts into pluripotent stem cells, but this is a slow and inefficient process. The most successful method to date for the reprogramming of adult fibroblasts to a pluripotent stem cell-like state is the use of a single transcription factor, Oct4, a protein encoded by the Pou5f1 (Oct4) gene. This is a gene from the POU domain transcription factor family. Pou5f1 is a transcription factor expressed in the germline cells of both sexes. This gene contains five domains: a DNA binding domain (DBD), a second transactivation domain (TAD2), a third transactivation domain (TAD3), a fourth domain (N-terminal domain) and a C-terminal domain. The domains that recognize a specific DNA sequence are located at the N-terminus, and the C-terminus contains the dimerization domain. POU5F1 protein is known to be a nuclear-localized transcription factor. Recent reports demonstrate that the introduction of a single transcription factor, Oct4, can reprogram somatic cells into a pluripotent state. However, its success rate is low, as only a small fraction of cells become converted. Furthermore, the method is not applicable to a broad range of cell types.





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Football Manager 2011. DUTCH.LTC Repackl

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