2009
DOI: 10.1073/pnas.0904825106
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Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-Myc expression for efficient human iPSC induction and differentiation

Abstract: Human-induced pluripotent stem cells (hiPSCs) are generated from somatic cells by ectopic expression of the 4 reprogramming factors (RFs) Oct-4, Sox2, Klf4, and c-Myc. To better define the stoichiometric requirements and dynamic expression patterns required for successful hiPSC induction, we generated 4 bicistronic lentiviral vectors encoding the 4 RFs co-expressed with discernable fluorescent proteins. Using this system, we define the optimal stoichiometry of RF expression to be highly sensitive to Oct4 dosag… Show more

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Cited by 266 publications
(258 citation statements)
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“…In addition, the transcription factor Sox-2 regulates the complex transcriptional network that maintains the unique characteristics of embryonic stem cells [30] and the anti-apoptosis property of human cancer stem cells [31]. Literature data show that expression of both these transcription factors is modified in an expanding list of cancers [32,33]. In humans, the normal ovarian and FT epithelia are characterized by negative or weak Oct4 and Sox-2 expression, that are conversely greatly enhanced during malignant transformation [18,19].…”
Section: Discussionmentioning
confidence: 99%
“…In addition, the transcription factor Sox-2 regulates the complex transcriptional network that maintains the unique characteristics of embryonic stem cells [30] and the anti-apoptosis property of human cancer stem cells [31]. Literature data show that expression of both these transcription factors is modified in an expanding list of cancers [32,33]. In humans, the normal ovarian and FT epithelia are characterized by negative or weak Oct4 and Sox-2 expression, that are conversely greatly enhanced during malignant transformation [18,19].…”
Section: Discussionmentioning
confidence: 99%
“…The amount of Oct-4 expression has been confirmed to play a crucial role in embryonic stem cells and its upregulation or downregulation completely change the pluripotent cell phenotype. An increase in the expression of Oct-4 enhances the relative ratio of Sox2, Klf4, or c-myc and consistently reduces the colony generation efficiency of human-induced pluripotent stem cells (hiPSC) up to more than 5-fold (88). Similarly, the loss of expression is associated with cell differentiation, and the abnormal expression is often used as a marker of embryonal cancer.…”
Section: Regulatory Mechanisms For Tumor Stem Cellsmentioning
confidence: 99%
“…As a master regulator of pluripotency, Oct4 was one of the original four factors utilized by Yamanaka and colleagues in the generation of iPSC in both mouse and human Takahashi and Yamanaka, 2006). As seen in Oct4 over-expression and downregulation experiments in ESC, the precise level of Oct4 in combination with other reprogramming factors is also essential for efficient generation of iPSC (Papapetrou et al, 2009). Using bicistronic vectors, Papapetrou et al (2009) showed that a 3-fold higher expression of Oct4 compared to Sox2, Klf4 and c-Myc enhanced iPSC generation (Papapetrou et al, 2009).…”
Section: Oct4mentioning
confidence: 99%
“…As seen in Oct4 over-expression and downregulation experiments in ESC, the precise level of Oct4 in combination with other reprogramming factors is also essential for efficient generation of iPSC (Papapetrou et al, 2009). Using bicistronic vectors, Papapetrou et al (2009) showed that a 3-fold higher expression of Oct4 compared to Sox2, Klf4 and c-Myc enhanced iPSC generation (Papapetrou et al, 2009). Interestingly, overexpression of Oct4 alone was sufficient to induce reprogramming in neural stem cells that already express high endogenous level of Sox2, cMyc and Klf4 (Kim et al, 2009b;Kim et al, 2009c).…”
Section: Oct4mentioning
confidence: 99%
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