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Cell. 2014 Feb 13;156(4):649-62. doi: 10.1016/j.cell.2014.01.020. Epub 2014 Jan 30.

Nonstochastic reprogramming from a privileged somatic cell state.

Author information

1
Department of Cell Biology, Yale University, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA. Electronic address: shangqin.guo@yale.edu.
2
Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA; Department of Cell Biology, Second Military Medical University, Shanghai 200433, China.
3
Department of Pediatrics, Yale University, New Haven, CT 06520, USA.
4
Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA; Department of Genetics, Yale University, New Haven, CT 06520, USA.
5
Department of Cell Biology, Yale University, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA.
6
Department of Immunobiology, Yale Flow Cytometry Core Facility, Yale University, New Haven, CT 06520, USA.
7
Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA; Department of Genetics, Yale University, New Haven, CT 06520, USA; Yale Comprehensive Cancer Center, Yale University, New Haven, CT 06520, USA.
8
Department of Pediatrics, Yale University, New Haven, CT 06520, USA; Department of Genetics, Yale University, New Haven, CT 06520, USA; Department of Pathology, Yale University, New Haven, CT 06520, USA.
9
Department of Cell Biology, Yale University, New Haven, CT 06520, USA; Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA; Department of Laboratory Medicine, Yale University, New Haven, CT 06520, USA.
10
Yale Stem Cell Center, Yale University, New Haven, CT 06520, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA; Yale Comprehensive Cancer Center, Yale University, New Haven, CT 06520, USA.

Abstract

Reprogramming somatic cells to induced pluripotency by Yamanaka factors is usually slow and inefficient and is thought to be a stochastic process. We identified a privileged somatic cell state, from which acquisition of pluripotency could occur in a nonstochastic manner. Subsets of murine hematopoietic progenitors are privileged whose progeny cells predominantly adopt the pluripotent fate with activation of endogenous Oct4 locus after four to five divisions in reprogramming conditions. Privileged cells display an ultrafast cell cycle of ∼8 hr. In fibroblasts, a subpopulation cycling at a similar ultrafast speed is observed after 6 days of factor expression and is increased by p53 knockdown. This ultrafast cycling population accounts for >99% of the bulk reprogramming activity in wild-type or p53 knockdown fibroblasts. Our data demonstrate that the stochastic nature of reprogramming can be overcome in a privileged somatic cell state and suggest that cell-cycle acceleration toward a critical threshold is an important bottleneck for reprogramming. PAPERCLIP:

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PMID:
24486105
PMCID:
PMC4318260
DOI:
10.1016/j.cell.2014.01.020
[Indexed for MEDLINE]
Free PMC Article
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