Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase
Author(s)Buganim, Yosef; Faddah, Dina A.; Cheng, Albert W.; Itskovich, Elena; Markoulaki, Styliani; Ganz, Kibibi; van Oudenaarden, Alexander; Jaenisch, Rudolf; Klemm, Sandy Lee; van Oudenaarden, Alexander; ... Show more Show less
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During cellular reprogramming, only a small fraction of cells become induced pluripotent stem cells (iPSCs). Previous analyses of gene expression during reprogramming were based on populations of cells, impeding single-cell level identification of reprogramming events. We utilized two gene expression technologies to profile 48 genes in single cells at various stages during the reprogramming process. Analysis of early stages revealed considerable variation in gene expression between cells in contrast to late stages. Expression of Esrrb, Utf1, Lin28, and Dppa2 is a better predictor for cells to progress into iPSCs than expression of the previously suggested reprogramming markers Fbxo15, Fgf4, and Oct4. Stochastic gene expression early in reprogramming is followed by a late hierarchical phase with Sox2 being the upstream factor in a gene expression hierarchy. Finally, downstream factors derived from the late phase, which do not include Oct4, Sox2, Klf4, c-Myc, and Nanog, can activate the pluripotency circuitry.
DepartmentMassachusetts Institute of Technology. Computational and Systems Biology Program; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science; Massachusetts Institute of Technology. Department of Physics; Whitehead Institute for Biomedical Research
Buganim, Yosef, Dina A. Faddah, Albert W. Cheng, Elena Itskovich, Styliani Markoulaki, Kibibi Ganz, Sandy L. Klemm, Alexander van Oudenaarden, and Rudolf Jaenisch. “Single-Cell Expression Analyses During Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase.” Cell 150, no. 6 (September 2012): 1209–1222. © 2012 Elsevier Inc.
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