Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase
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 expressio...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/91944 |
| _version_ | 1826201073679859712 |
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| author | Buganim, Yosef Faddah, Dina A. Itskovich, Elena Markoulaki, Styliani Ganz, Kibibi van Oudenaarden, Alexander Jaenisch, Rudolf Klemm, Sandy Lee van Oudenaarden, Alexander Cheng, Albert Wu |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Buganim, Yosef Faddah, Dina A. Itskovich, Elena Markoulaki, Styliani Ganz, Kibibi van Oudenaarden, Alexander Jaenisch, Rudolf Klemm, Sandy Lee van Oudenaarden, Alexander Cheng, Albert Wu |
| author_sort | Buganim, Yosef |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:46:11Z |
| format | Article |
| id | mit-1721.1/91944 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:46:11Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/919442022-10-01T05:52:01Z Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase Buganim, Yosef Faddah, Dina A. Itskovich, Elena Markoulaki, Styliani Ganz, Kibibi van Oudenaarden, Alexander Jaenisch, Rudolf Klemm, Sandy Lee van Oudenaarden, Alexander Cheng, Albert Wu Massachusetts 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 Klemm, Sandy Lee Faddah, Dina A. Cheng, Albert W. van Oudenaarden, Alexander Jaenisch, Rudolf 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. National Science Foundation (U.S.). Graduate Research Fellowship Program Vertex Pharmaceuticals Incorporated (Vertex Scholar Award) Jerome and Florence Brill Graduate Student Fellowship Croucher Foundation (Croucher and Ludwig Research Fellowship) National Institutes of Health (U.S.). Pioneer Award (1DP1OD003936) National Cancer Institute (U.S.). Physical Sciences-Oncology Center (U54CA143874) National Institutes of Health (U.S.) (Grant HD 045022) National Institutes of Health (U.S.) (Grant R37CA084198) 2014-11-26T20:00:42Z 2014-11-26T20:00:42Z 2012-09 2012-07 Article http://purl.org/eprint/type/JournalArticle 00928674 1097-4172 http://hdl.handle.net/1721.1/91944 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. en_US http://dx.doi.org/10.1016/j.cell.2012.08.023 Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier |
| spellingShingle | Buganim, Yosef Faddah, Dina A. Itskovich, Elena Markoulaki, Styliani Ganz, Kibibi van Oudenaarden, Alexander Jaenisch, Rudolf Klemm, Sandy Lee van Oudenaarden, Alexander Cheng, Albert Wu Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase |
| title | Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase |
| title_full | Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase |
| title_fullStr | Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase |
| title_full_unstemmed | Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase |
| title_short | Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase |
| title_sort | single cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase |
| url | http://hdl.handle.net/1721.1/91944 |
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