Resetting Transcription Factor Control Circuitry toward Ground-State Pluripotency in Human
Wellcome/MRC Cambridge Stem Cell Institute · University of Cambridge · +8 more institutions
Abstract
Current human pluripotent stem cells lack the transcription factor circuitry that governs the ground state of mouse embryonic stem cells (ESC). Here, we report that short-term expression of two components, NANOG and KLF2, is sufficient to ignite other elements of the network and reset the human pluripotent state. Inhibition of ERK and protein kinase C sustains a transgene-independent rewired state. Reset cells self-renew continuously without ERK signaling, are phenotypically stable, and are karyotypically intact. They differentiate in vitro and form teratomas in vivo. Metabolism is reprogrammed with activation of mitochondrial respiration as in ESC. DNA methylation is dramatically reduced and transcriptome…
Citation impact
- FWCI
- 40.83
- Percentile
- 100%
- References
- 70
Authors
13- YTYasuhiro TakashimaCorresponding
Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, Japan Science and Technology Agency, Medical Research Council
- GGGe Guo
Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, Medical Research Council
- RLRemco Loos
European Bioinformatics Institute, Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, Wellcome Trust, Medical Research Council
- JNJennifer Nichols
Wellcome/MRC Cambridge Stem Cell Institute, University of Cambridge, Medical Research Council
- GFGabriella Ficz
University of London
Topics & keywords
- Biology
- Cell biology
- Homeobox protein NANOG
- Induced pluripotent stem cell
- Transcription factor
- Rex1
- Embryonic stem cell
- Stem cell
- Life in Land