Role of the murine reprogramming factors in the induction of pluripotency

By Rupa Sridharan, J. Tchieu, Mike J. Mason, Robin Yachechko, Edward Kuoy, Steve Horvath, Qing Zhou, Kathrin Plath. Cell, 2009

693 citations recorded by the source corpus.

Summary Induced pluripotent stem (iPS) cells can be obtained from fibroblasts upon expression of Oct4, Sox2, Klf4 and c-Myc. To understand how these factors induce pluripotency, we carried out genome-wide analyses of their promoter binding and expression in iPS and partially reprogrammed cells. We find that target genes of the four factors strongly overlap in iPS and embryonic stem (ES) cells. In partially reprogrammed cells, many genes co-occupied by c-Myc and any of the other three factors already show an ES-like binding and expression pattern. In contrast, genes that are specifically co-bound by Oct4, Sox2 and Klf4 in ES cells and encode pluripotency regulators severely lack binding and transcriptional activation. Among the four factors, c-Myc promotes the most ES cell-like transcription pattern when expressed individually in fibroblasts. These data uncover temporal and separable contributions of the four factors during the reprogramming process and indicate that ectopic c-Myc predominantly acts before pluripotency regulators are activated.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/69c55ed4b7c3c471ec512e9012a2b30931cccb3f

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Citations in the corpus

A Small Molecule Inhibitor of Tgf-β Signaling Replaces Sox2 in Reprogramming by Inducing Nanog (2009, background): “Our observation that a one-day treatment with RepSox can relieve the requirement for transgenic Sox2 indicates that unlike reprogramming using transgenic Oct4, Klf4, and Sox2, where each transgene must be expressed for several days (Sridharan et al., 2009; Stadtfeld et al., 2008), small molecules ca”
Direct cell reprogramming is a stochastic process amenable to acceleration (2009, background): “14 Sridharan, R. et al., Role of the murine reprogramming factors in the induction of pluripotency. Cell 136 (2), 364-377 (2009).”
Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration (2011, background): “Which factors? Since the initial finding that fibroblasts can be reprogrammed to pluripotency with the four transcription factors OCT4, SOX2, Kruppel-like factor 4 (KLF4) and MY”
Nanog Is the Gateway to the Pluripotent Ground State (2009, neutral): “However, Nanog is expressed weakly or not at all in incompletely reprogrammed cells that fail to activate properly the endogenous pluripotent transcriptional circuitry (Silva et al., 2008; Sridharan et al., 2009; Takahashi and Yamanaka, 2006).”
Naive and primed pluripotent states. (2009, methodology): “In line with this idea, use of 2i plus Lif facilitates the isolation of authentic induced pluripotent stem cell (iPSC) lines with full pluripotent capacity (Guo et al., 2009; Silva et al., 2008; Sridharan et al., 2009).”
Distinct Epigenomic Landscapes of Pluripotent and Lineage-committed Human Cells (2010, result): “Despite the wider coverage of H3K9me3 in IMR90 cells, there is more overlap between iPSCs and hESCs (H3K9me3 = 105 MB, H3K27me3 = 102 MB) than between IMR90 cells and hESCs (H3K9me3 = 76 MB, H3K27me3 = 68 MB), indicating that reprogramming has resulted in an epigenome that is more similar to the hES”
Facilitators and Impediments of the Pluripotency Reprogramming Factors’ Initial Engagement with the Genome (2012, neutral): “In contrast, c-Myc binds almost exclusively to promoters in ES cells (Figure 2C) (Chen et al., 2008; Kim et al., 2008; Sridharan et al., 2009).”
Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation (2009, background): “The requirement for a specific factor stoichiometry is also consistent with the finding that the 4 RFs co-occupy promoters of many genes in iPSCs and ESCs and may co-operatively act during reprogramming (30).”