Generation of human induced pluripotent stem cells from dermal fibroblasts

Generation of human induced pluripotent stem cells from dermal fibroblasts

February 26, 2008 | W. E. Lowry, L. Richter, R. Yachechko, A. D. Pyle, J. Tchieu, R. Sridharan, A. T. Clark, K. Plath
This study describes a method to generate human induced pluripotent stem (iPS) cells from dermal fibroblasts by ectopic expression of defined transcription factors: KLF4, OCT4, SOX2, and C-MYC. The resulting iPS cells are morphologically and genetically indistinguishable from human embryonic stem cells (HESCs). They share a nearly identical gene-expression profile with established HESC lines and are derived from the donor material, indicating no contamination. Karyotypic analyses show that reprogramming does not induce chromosomal abnormalities. The iPS cells can differentiate into lineages representing the three embryonic germ layers, demonstrating their pluripotency. These findings represent a significant step toward generating patient-specific pluripotent stem cells. The use of defined factors to reprogram cells may be key to routine nuclear reprogramming of human somatic cells. The study also highlights the importance of TRA-1–81 staining for identifying reprogrammed cells and the role of defined factors in reprogramming. The results suggest that the reprogramming process is conserved across species and that the specific role of each transcription factor remains to be determined. Future challenges include developing methods to reprogram fibroblasts from patients with diseases and showing that reprogrammed cells can differentiate into functional cell types. The study provides a foundation for further research into the mechanisms of reprogramming and its potential applications in regenerative medicine.This study describes a method to generate human induced pluripotent stem (iPS) cells from dermal fibroblasts by ectopic expression of defined transcription factors: KLF4, OCT4, SOX2, and C-MYC. The resulting iPS cells are morphologically and genetically indistinguishable from human embryonic stem cells (HESCs). They share a nearly identical gene-expression profile with established HESC lines and are derived from the donor material, indicating no contamination. Karyotypic analyses show that reprogramming does not induce chromosomal abnormalities. The iPS cells can differentiate into lineages representing the three embryonic germ layers, demonstrating their pluripotency. These findings represent a significant step toward generating patient-specific pluripotent stem cells. The use of defined factors to reprogram cells may be key to routine nuclear reprogramming of human somatic cells. The study also highlights the importance of TRA-1–81 staining for identifying reprogrammed cells and the role of defined factors in reprogramming. The results suggest that the reprogramming process is conserved across species and that the specific role of each transcription factor remains to be determined. Future challenges include developing methods to reprogram fibroblasts from patients with diseases and showing that reprogrammed cells can differentiate into functional cell types. The study provides a foundation for further research into the mechanisms of reprogramming and its potential applications in regenerative medicine.
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