Peer-Reviewed Publication
Cell Rep2016;15(12):2597-607.June 21, 2016Journal Article
RNAi Reveals Phase-Specific Global Regulators of Human Somatic Cell Reprogramming.
Cheng-Xu Delon Toh1, Jun-Wei Chan2, Zheng-Shan Chong2, Hao Fei Wang3, Hong Chao Guo4, Sandeep Satapathy2, Dongrui Ma5, Germaine Yen Lin Goh6, Ekta Khattar7, Lin Yang8, Vinay Tergaonkar9, Young-Tae Chang10, James J Collins11, George Q Daley12, Keng Boon Wee13, Chadi A El Farran3, Hu Li14, Yoon-Pin Lim15, Frederic A Bard16, Yuin-Han Loh17
1Epigenetics and Cell Fates Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore.
2Epigenetics and Cell Fates Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.
3Epigenetics and Cell Fates Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore; Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
4Epigenetics and Cell Fates Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore; College of Life Sciences, Nankai University, Tianjin 300071, China.
5Research and Development Unit (RDU), National Heart Centre Singapore, 5(th) Hospital Drive, Singapore 169609, Singapore.
6Membrane Traffic Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.
7Division of Cancer Genetics and Therapeutics, Laboratory of NF-κB Signaling, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore.
8Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02114, USA; Howard Hughes Medical Institute, Boston, MA 02114, USA.
9Division of Cancer Genetics and Therapeutics, Laboratory of NF-κB Signaling, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.
10Lab of Bioimaging Probe Development, A(∗)STAR Singapore Bioimaging Consortium (SBIC), 11 Biopolis Way Helios, Singapore 138673, Singapore; Department of Chemistry and MedChem Program, Life Sciences Institute, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
11Howard Hughes Medical Institute, Boston, MA 02114, USA; Institute for Medical Engineering and Science Department of Biological Engineering, and Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
12Howard Hughes Medical Institute, Boston, MA 02114, USA; Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children's Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Boston, MA 02115, USA; Manton Center for Orphan Disease Research, Boston, MA 02115, USA.
13A(∗)STAR Institute of High Performance Computing (IHPC), Connexis, Singapore 138632, Singapore; A(∗)STAR Bioinformatics Institute, Singapore 138671, Singapore.
14Center for Individualized Medicine, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: li.hu@mayo.edu.
15NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore; A(∗)STAR Bioinformatics Institute, Singapore 138671, Singapore. Electronic address: bchlyp@nus.edu.sg.
16Membrane Traffic Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.
17Epigenetics and Cell Fates Laboratory, A(∗)STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore; Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore. Electronic address: yhloh@imcb.a-star.edu.sg.
Abstract
Incomplete knowledge of the mechanisms at work continues to hamper efforts to maximize reprogramming efficiency. Here, we present a systematic genome-wide RNAi screen to determine the global regulators during the early stages of human reprogramming. Our screen identifies functional repressors and effectors that act to impede or promote the reprogramming process. Repressors and effectors form close…
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