Direct cell reprogramming is a stochastic process amenable to acceleration
| Autor: | Rudolf Jaenisch, Jacob H. Hanna, Menno P. Creyghton, Bernardo F. Pando, Jeroen S. van Zon, Christopher J. Lengner, Alexander van Oudenaarden, Krishanu Saha |
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| Rok vydání: | 2009 |
| Předmět: |
Pluripotent Stem Cells
Homeobox protein NANOG Time Factors Somatic cell Cellular differentiation Mice SCID Biology Models Biological Article Cell Line Kruppel-Like Factor 4 Mice 03 medical and health sciences 0302 clinical medicine SOX2 Animals Induced pluripotent stem cell Cell potency 030304 developmental biology Genetics 0303 health sciences Multidisciplinary Gene Expression Regulation Developmental Cell Differentiation Cellular Reprogramming Cell biology KLF4 Reprogramming Cell Division 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming by these transcription factors is a continuous stochastic process where almost all mouse donor cells eventually give rise to iPS cells on continued growth and transcription factor expression. Additional inhibition of the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPS cell formation that was directly proportional to the increase in cell proliferation. In contrast, Nanog overexpression accelerated reprogramming in a predominantly cell-division-rate-independent manner. Quantitative analyses define distinct cell-division-rate-dependent and -independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprogramming to pluripotency. |
| Databáze: | OpenAIRE |
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