Biochemistry & Molecular Pharmacology
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Animals; Cells, Cultured; Cellular Reprogramming; Chromosomal Proteins, Non-Histone; Cyclin-Dependent Kinase Inhibitor p16; Embryonic Stem Cells; Epidermal Growth Factor; *Genome; Hepatocyte Nuclear Factor 4; Homeodomain Proteins; Induced Pluripotent Stem Cells; Inositol 1,4,5-Trisphosphate Receptors; Membrane Glycoproteins; Mice; NF-E2 Transcription Factor, p45 Subunit; Neoplasm Proteins; Nerve Tissue Proteins; Otx Transcription Factors; Protein Disulfide-Isomerases; Signal Transduction; Suppressor of Cytokine Signaling Proteins; Trans-Activators; Transcription Factors; Transcription Factors, TFII; Transcriptome; Tumor Suppressor Proteins
Cell and Developmental Biology | Genetics and Genomics | Genomics
Although transcriptome analysis can uncover the molecular changes that occur during induced reprogramming, the functional requirements for a given factor during stepwise cell-fate transitions are left unclear. Here, we used a genome-wide RNAi screen and performed integrated transcriptome analysis to identify key genes and cellular events required at the transition steps in reprogramming. Genes associated with cell signaling pathways (e.g., Itpr1, Itpr2, and Pdia3) constitute the major regulatory networks before cells acquire pluripotency. Activation of a specific gene set (e.g., Utf1 or Tdgf1) is important for mature induced pluripotent stem cell formation. Strikingly, a major proportion of RNAi targets ( approximately 53% to 70%) includes genes whose expression levels are unchanged during reprogramming. Among these non-differentially expressed genes, Dmbx1, Hnf4g, Nobox, and Asb4 are important, whereas Nfe2, Cdkn2aip, Msx3, Dbx1, Lzts1, Gtf2i, and Ankrd22 are roadblocks to reprogramming. Together, our results provide a wealth of information about gene functions required at transition steps during reprogramming.
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Citation: Cell Rep. 2014 Jul 24;8(2):327-37. doi: 10.1016/j.celrep.2014.07.002. Epub 2014 Jul 17. Link to article on publisher's site
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Yang, Chao-Shun; Chang, Kung-Yen; and Rana, Tariq M., "Genome-wide functional analysis reveals factors needed at the transition steps of induced reprogramming" (2014). GSBS Student Publications. 1919.