Nanog Is the Gateway to the Pluripotent Ground State

Silva, Fernando; Nichols, Jennifer; Theunissen, Thorold W.; Guo, Ge; Oosten, Anouk L. van; Barrandon, Ornella; Wray, Jason; Yamanaka, Shinya; Chambers, Ian; Smith, Austin

doi:10.1016/j.cell.2009.07.039

Cited by 939 publications

(1,047 citation statements)

References 55 publications

(81 reference statements)

Supporting

Mentioning

970

Contrasting

Unclassified

Order By: Relevance

“…For example, some reports proposed the expression of early differentiation markers as a characteristic of EpiSCs [3,17], whereas others reported the absence of these markers. Furthermore, some studies found that transcription factor overexpression was required for reversion of EpiSCs to an mESC-like state [5][6][7][8], whereas others showed reversion could be achieved by somewhat milder means just using stringent mESC culture conditions [4,9,10].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Distinct Developmental Ground States of Epiblast Stem Cell Lines Determine Different Pluripotency Features

et al. 2011

View full text Add to dashboard Cite

Epiblast stem cells (EpiSCs) are pluripotent stem cells derived from mouse postimplantation embryos at embryonic day (E) 5.5-E7.5 at the onset of gastrulation, which makes them a valuable tool for studying mammalian postimplantation development in vitro. EpiSCs can also be reprogrammed into a mouse embryonic stem cell (mESC)-like state. Some reports have shown that the reversion of EpiSCs requires transcription factor overexpression, whereas others have suggested that use of stringent mESC culture conditions alone is sufficient for the reversion of EpiSCs. To clarify these discrepancies, we systematically compared a panel of independent EpiSC lines. We found that-regardless of the embryonic day of derivation-the different EpiSC lines shared a number of defining characteristics such as the ability to form teratomas. However, despite use of standard EpiSC culture conditions, some lines exhibited elevated expression of genes associated with mesendodermal differentiation. Pluripotency (Oct4) and mesodermal (Brachyury) marker genes were coexpressed in this subset of lines. Interestingly, the expression of mesendodermal marker genes was negatively correlated with the cells' ability to efficiently undergo neural induction. Moreover, these mesodermal marker gene-expressing cell lines could not be efficiently reverted to an mESC-like state by using stringent mESC culture conditions. Conversely, Brachyury overexpression diminished the reversion efficiency in otherwise Brachyury-negative lines. Overall, our data suggest that different EpiSC lines may undergo self-renewal into distinct developmental states, a finding with important implications for functional readouts such as reversion of EpiSCs to an mESC-like state as well as directed differentiation. STEM CELLS

show abstract

Section: Discussionmentioning

confidence: 99%

“…They present conflicting views on their ability to revert to a state similar to that of mESCs (a mESClike state). Some studies suggest that transcription factor overexpression is required for the reversion of EpiSCs [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Distinct Developmental Ground States of Epiblast Stem Cell Lines Determine Different Pluripotency Features

et al. 2011

View full text Add to dashboard Cite

show abstract

“…However, transcriptome studies demonstrated that expression of OCT4, NANOG, and SOX2 was significantly lower in haGSC than in hESC, consistent with the notion that the promoter regions of OCT4 and NANOG were only partially demethylated in haGSC. As full demethylation of these promoters is an important criterion of complete pluripotency [30,31], this suggests that haGSC may only have acquired a partially reprogrammed state.…”

Section: Can In Vitro Culture Convert Germline Stem/progenitor Cells mentioning

confidence: 99%

Concise Review: Culture Mediated Changes in Fate and/or Potency of Stem Cells

2011

View full text Add to dashboard Cite

Although Gurdon demonstrated already in 1958 that the nucleus of intestinal epithelial cells could be reprogrammed to give rise to adult frogs, the field of cellular reprogramming has only recently come of age with the description by Takahashi and Yamanaka in 2006, which defined transcription factors can reprogram fibroblasts to an embryonic stem cell-like fate. With the mounting interest in the use of human pluripotent stem cells and culture-expanded somatic stem/progenitor cells, such as mesenchymal stem cells, increasing attention has been given to the effect of changes in the in vitro microenvironment on the fate of stem cells. These studies have demonstrated that changes in culture conditions may change the potency of pluripotent stem cells or reprogram adult stem/progenitor cells to endow them with a broader differentiation potential. The mechanisms underlying these fate and potency changes by ex vivo culture should be further investigated and considered when designing clinical therapies with stem/progenitor cells. STEM CELLS

show abstract

“…11,12 Multipotentiality of stem cells has been strongly associated with expression of certain transcription factors such as Nanog, Oct3/4, Klf4, and Sox2. 13,14 It has been proposed that Nanog has a key role in maintaining embryonic stem cell pluripotency 15 ; however, stem cell pluripotency is also expressed in adult stem cells. 8 The ability of the progenitor cells to participate in scar formation, in particular insofar as maturation of fibroblasts into myofibroblasts, decreases with age.…”

mentioning

confidence: 99%

Defective Myofibroblast Formation from Mesenchymal Stem Cells in the Aging Murine Heart

Cieslik

Trial

Entman

2011

The American Journal of Pathology

View full text Add to dashboard Cite

Cardiac fibroblasts are the most prevalent cell type in the heart. These cells exert a critical role in regulating normal myocardial function and in the adverse myocardial remodeling that occurs after myocardial infarction (MI). 1 Irreversible cardiomyocyte damage owing to cessation of oxygen supply during MI leads to necrosis, which stimulates inflammatory reactions that trigger reparative pathways and activate cells to form a scar. Cytokines released by inflammatory infiltrating leukocytes promote endogenous mesenchymal stem cell (MSC) proliferation and migration toward the infarct site, followed by differentiation into fibroblasts that deposit scar-forming collagen. The fibroblasts mature into myofibroblasts, expressing scar-contracting ␣-smooth muscle actin (␣-SMA). 2 Resident fibroblasts also become activated and participate in this process. After several weeks, a mature scar is formed, and most of the myofibroblasts undergo apoptosis. [3][4][5] We have previously established in a model of mouse MI that, compared with young animals, aged mice demonstrate greater infarct expansion and less effective myocardial repair. 6 Defective scar formation arises from a decreased number of myofibroblasts and diminished collagen deposition in the infarct, which results in a structurally unstable scar formed by loose connective tissue. 7 Evidence indicates that multipotent cells can be generated in vitro from several adult organs including the heart. 8 Tissue-resident progenitor cells of mesenchymal origin can differentiate into myogenic, adipocytic, chondrocytic, osteoblastic, and fibroblastic lineages. 9 -11 The potential of those stem cells to differentiate decreases

show abstract

Nanog Is the Gateway to the Pluripotent Ground State

Cited by 939 publications

References 55 publications

Distinct Developmental Ground States of Epiblast Stem Cell Lines Determine Different Pluripotency Features

Distinct Developmental Ground States of Epiblast Stem Cell Lines Determine Different Pluripotency Features

Concise Review: Culture Mediated Changes in Fate and/or Potency of Stem Cells

Defective Myofibroblast Formation from Mesenchymal Stem Cells in the Aging Murine Heart

Contact Info

Product

Resources

About