The <i>Sox-2</i> Regulatory Regions Display Their Activities in Two Distinct Types of Multipotent Stem Cells

Miyagi, Satoru; Saito, Tetsuichiro; Mizutani, Ken-ichi; Masuyama, Norihisa; Gotoh, Yukiko; Iwama, Atsushi; Nakauchi, Hiromitsu; Masui, Shinji; Niwa, Hitoshi; Nishimoto, Masazumi; Muramatsu, Masami; Okuda, Akihiko

doi:10.1128/mcb.24.10.4207-4220.2004

Cited by 92 publications

(107 citation statements)

References 58 publications

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“…Our results indicate that it is precisely this upstream distal enhancer that is activated in mammospheres, as a luciferase reporter with this enhancer is strongly induced upon sphere formation. The upstream enhancer was strongly activated in undifferentiated embryonic stem cells and its activity was lost upon differentiation (Tomioka et al, 2002), it is the same behaviour as observed in multipotent neural stem cells (Miyagi et al, 2004;Miyagi et al, 2006). In embryonic stem cells, a non-consensus octamer-binding site in the enhancer is occupied by Oct3/4-Sox2 dimers, however, as we did not observe Oct4 expression in mammospheres, a different mechanism must operate.…”

Section: Sox2 Activation In Breast Cancer Stem Cellssupporting

confidence: 78%

Sox2 expression in breast tumours and activation in breast cancer stem cells

Leis¹,

Eguiara²,

et al. 2011

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The cancer stem cell (CSC) model does not imply that tumours are generated from transformed tissue stem cells. The target of transformation could be a tissue stem cell, a progenitor cell, or a differentiated cell that acquires selfrenewal ability. The observation that induced pluripotency reprogramming and cancer are related has lead to the speculation that CSCs may arise through a reprogramming-like mechanism. Expression of pluripotency genes (Oct4, Nanog and Sox2) was tested in breast tumours by immunohistochemistry and it was found that Sox2 is expressed in early stage breast tumours. However, expression of Oct4 or Nanog was not found. Mammosphere formation in culture was used to reveal stem cell properties, where expression of Sox2, but not Oct4 or Nanog, was induced. Over-expression of Sox2 increased mammosphere formation, effect dependent on continuous Sox2 expression; furthermore, Sox2 knockdown prevented mammosphere formation and delayed tumour formation in xenograft tumour initiation models. Induction of Sox2 expression was achieved through activation of the distal enhancer of Sox2 promoter upon sphere formation, the same element that controls Sox2 transcription in pluripotent stem cells. These findings suggest that reactivation of Sox2 represents an early step in breast tumour initiation, explaining tumour heterogeneity by placing the tumour-initiating event in any cell along the axis of mammary differentiation.

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Section: Sox2 Activation In Breast Cancer Stem Cellssupporting

confidence: 78%

Sox2 expression in breast tumours and activation in breast cancer stem cells

Leis¹,

Eguiara²,

et al. 2011

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“…Such mechanisms possibly include modulatory effects at promoter and/or enhancer regions of various transcription factors. For example, two distinct Sox2 enhancers are active in multipotent neural progenitors but cease to function in differentiated cells (Zappone et al, 2000;Miyagi et al, 2004). The mouse Pax6 gene has three promoters under the control of at least six different enhancers, directing Pax6 expression in distinct tissues (reviewed by Morgan, 2004).…”

Section: Discussionmentioning

confidence: 99%

Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone

Tonchev¹,

Yamashima²,

Sawamoto³

2006

Neuroscience

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Abstract-The anterior subventricular zone of the adult mammalian brain contains progenitor cells which are upregulated after cerebral ischemia. We have previously reported that while a part of the progenitors residing in adult monkey anterior subventricular zone travels to the olfactory bulb, many of these cells sustain location in the anterior subventricular zone for months after injury, exhibiting a phenotype of either neural or neuronal precursors. Here we show that ischemia increased the numbers of anterior subventricular zone progenitor cells expressing developmentally regulated transcription factors including Pax6 (paired-box 6), Emx2 (empty spiracles-homeobox 2), Sox 1-3 (sex determining region Y-box 1-3), Ngn1 (neurogenin 1), Dlx1,5 (distalless-homeobox 1,5), Olig1,3 (oligodendrocyte lineage gene 1,3) and Nkx2.2 (Nk-box 2.2), as compared with control brains. Analysis of transcription factor protein expression by sustained neural or neuronal precursors in anterior subventricular zone revealed that these two cell types were positive for characteristic sets of transcription factors. The proteins Pax6, Emx2, Sox2,3 and Olig1 were predominantly localized to dividing neural precursors while the factors Sox1, Ngn1, Dlx1,5, Olig2 and Nkx2.2 were mainly expressed by neuronal precursors. Further, differences between monkeys and non-primate mammals emerged, related to expression patterns of Pax6, Olig2 and Dlx2. Our results suggest that a complex network of developmental signals might be involved in the specification of primate progenitor cells.

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“…Indirect immunocytochemistry was carried out as previously described [26] with cells that had been cultured on coverslips coated with poly-D-lysine and laminin. For 5-Bromo-2 0 -deoxyuridine (BrdU) labeling experiments, cells were treated with 10 lg/ml BrdU for 30 minutes.…”

Section: Immunocytochemistrymentioning

confidence: 99%

Differential Requirement for Nucleostemin in Embryonic Stem Cell and Neural Stem Cell Viability

et al. 2009

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Stem cells have the remarkable ability to self-renew and to generate multiple cell types. Nucleostemin is one of proteins that are enriched in many types of stem cells. Targeted deletion of nucleostemin in the mouse results in developmental arrest at the implantation stage, indicating that nucleostemin is crucial for early embryogenesis. However, the molecular basis of nucleostemin function in early mouse embryos remains largely unknown, and the role of nucleostemin in tissue stem cells has not been examined by gene targeting analyses due to the early embryonic lethality of nucleostemin null animals. To address these questions, we generated inducible nucleostemin null embryonic stem (ES) cells in which both alleles of nucleostemin are disrupted, but nucleostemin cDNA under the control of a tetracycline-responsive transcriptional activator is introduced into the Rosa26 locus. We show that loss of nucleostemin results in reduced cell proliferation and increased apoptosis in both ES cells and ES cell-derived neural stem/progenitor cells. The reduction in cell viability is much more profound in ES cells than in neural stem/progenitor cells, an effect that is mediated at least in part by increased induction and accumulation of p53 and/or activated caspase-3 in ES cells than in neural stem/progenitor cells.

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The Sox-2 Regulatory Regions Display Their Activities in Two Distinct Types of Multipotent Stem Cells

Cited by 92 publications

References 58 publications

Sox2 expression in breast tumours and activation in breast cancer stem cells

Sox2 expression in breast tumours and activation in breast cancer stem cells

Transcription factor protein expression patterns by neural or neuronal progenitor cells of adult monkey subventricular zone

Differential Requirement for Nucleostemin in Embryonic Stem Cell and Neural Stem Cell Viability

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