The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection
Induced pluripotent stem cells (iPSCs) are commonly generated by transduction of Oct4, Sox2, Klf4, and Myc (OSKM) into cells. Although iPSCs are pluripotent, they frequently exhibit high variation in terms of quality, as measured in mice by chimera contribution and tetraploid complementation. Reliab...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/109508 https://orcid.org/0000-0001-8855-8647 |
| _version_ | 1826214288717512704 |
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| author | Buganim, Yosef Markoulaki, Styliani van Wietmarschen, Niek Wu, Tao Ganz, Kibibi Akhtar-Zaidi, Batool He, Yupeng Abraham, Brian J. Porubsky, David Kulenkampff, Elisabeth Shi, Linyu Gao, Qing Sarkar, Sovan Cohen, Malkiel Goldmann, Johanna Nery, Joseph R. Schultz, Matthew D. Ecker, Joseph R. Xiao, Andrew Lansdorp, Peter M. Hoke, Heather Ashley Jaenisch, Rudolf Faddah, Dina A. Young, Richard A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Buganim, Yosef Markoulaki, Styliani van Wietmarschen, Niek Wu, Tao Ganz, Kibibi Akhtar-Zaidi, Batool He, Yupeng Abraham, Brian J. Porubsky, David Kulenkampff, Elisabeth Shi, Linyu Gao, Qing Sarkar, Sovan Cohen, Malkiel Goldmann, Johanna Nery, Joseph R. Schultz, Matthew D. Ecker, Joseph R. Xiao, Andrew Lansdorp, Peter M. Hoke, Heather Ashley Jaenisch, Rudolf Faddah, Dina A. Young, Richard A. |
| author_sort | Buganim, Yosef |
| collection | MIT |
| description | Induced pluripotent stem cells (iPSCs) are commonly generated by transduction of Oct4, Sox2, Klf4, and Myc (OSKM) into cells. Although iPSCs are pluripotent, they frequently exhibit high variation in terms of quality, as measured in mice by chimera contribution and tetraploid complementation. Reliably high-quality iPSCs will be needed for future therapeutic applications. Here, we show that one major determinant of iPSC quality is the combination of reprogramming factors used. Based on tetraploid complementation, we found that ectopic expression of Sall4, Nanog, Esrrb, and Lin28 (SNEL) in mouse embryonic fibroblasts (MEFs) generated high-quality iPSCs more efficiently than other combinations of factors including OSKM. Although differentially methylated regions, transcript number of master regulators, establishment of specific superenhancers, and global aneuploidy were comparable between high- and low-quality lines, aberrant gene expression, trisomy of chromosome 8, and abnormal H2A.X deposition were distinguishing features that could potentially also be applicable to human. |
| first_indexed | 2024-09-23T12:56:50Z |
| format | Article |
| id | mit-1721.1/109508 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:56:50Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1095082022-09-28T11:05:50Z The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection Buganim, Yosef Markoulaki, Styliani van Wietmarschen, Niek Wu, Tao Ganz, Kibibi Akhtar-Zaidi, Batool He, Yupeng Abraham, Brian J. Porubsky, David Kulenkampff, Elisabeth Shi, Linyu Gao, Qing Sarkar, Sovan Cohen, Malkiel Goldmann, Johanna Nery, Joseph R. Schultz, Matthew D. Ecker, Joseph R. Xiao, Andrew Lansdorp, Peter M. Hoke, Heather Ashley Jaenisch, Rudolf Faddah, Dina A. Young, Richard A. Massachusetts Institute of Technology. Department of Biology Hoke, Heather Ashley Faddah, Dina Adel Young, Richard A Jaenisch, Rudolf Induced pluripotent stem cells (iPSCs) are commonly generated by transduction of Oct4, Sox2, Klf4, and Myc (OSKM) into cells. Although iPSCs are pluripotent, they frequently exhibit high variation in terms of quality, as measured in mice by chimera contribution and tetraploid complementation. Reliably high-quality iPSCs will be needed for future therapeutic applications. Here, we show that one major determinant of iPSC quality is the combination of reprogramming factors used. Based on tetraploid complementation, we found that ectopic expression of Sall4, Nanog, Esrrb, and Lin28 (SNEL) in mouse embryonic fibroblasts (MEFs) generated high-quality iPSCs more efficiently than other combinations of factors including OSKM. Although differentially methylated regions, transcript number of master regulators, establishment of specific superenhancers, and global aneuploidy were comparable between high- and low-quality lines, aberrant gene expression, trisomy of chromosome 8, and abnormal H2A.X deposition were distinguishing features that could potentially also be applicable to human. National Science Foundation (U.S.). Graduate Research Fellowship Program Whitehead Institute for Biomedical Research (Jerome and Florence Brill Graduate Student Fellowship) National Institutes of Health (U.S.) (grants HD 045022) National Institutes of Health (U.S.) (R37CA084198) Gordon and Betty Moore Foundation (GMBF3034) 2017-06-01T17:32:52Z 2017-06-01T17:32:52Z 2014-09 2014-03 Article http://purl.org/eprint/type/JournalArticle 1934-5909 http://hdl.handle.net/1721.1/109508 Buganim, Yosef, Styliani Markoulaki, Niek van Wietmarschen, Heather Hoke, Tao Wu, Kibibi Ganz, Batool Akhtar-Zaidi, et al. “The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection.” Cell Stem Cell 15, no. 3 (September 2014): 295–309. © 2014 Elsevier Inc. https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1016/j.stem.2014.07.003 Cell Stem Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Buganim, Yosef Markoulaki, Styliani van Wietmarschen, Niek Wu, Tao Ganz, Kibibi Akhtar-Zaidi, Batool He, Yupeng Abraham, Brian J. Porubsky, David Kulenkampff, Elisabeth Shi, Linyu Gao, Qing Sarkar, Sovan Cohen, Malkiel Goldmann, Johanna Nery, Joseph R. Schultz, Matthew D. Ecker, Joseph R. Xiao, Andrew Lansdorp, Peter M. Hoke, Heather Ashley Jaenisch, Rudolf Faddah, Dina A. Young, Richard A. The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection |
| title | The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection |
| title_full | The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection |
| title_fullStr | The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection |
| title_full_unstemmed | The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection |
| title_short | The Developmental Potential of iPSCs Is Greatly Influenced by Reprogramming Factor Selection |
| title_sort | developmental potential of ipscs is greatly influenced by reprogramming factor selection |
| url | http://hdl.handle.net/1721.1/109508 https://orcid.org/0000-0001-8855-8647 |
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