LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism

Cartwright, Peter; McLean, Cameron; Sheppard, Allan; Rivett, Duane; Jones, Karen L.; Dalton, Stephen

doi:10.1242/dev.01670

Cited by 667 publications

(610 citation statements)

References 51 publications

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“…Myc-dependent mechanisms are involved in the control of pluripotency and self-renewing capacity of murine embryonic stem cells [16], and in the expansion of neural progenitor cell populations and inhibition of differentiation [17; 18]. Several studies have demonstrated that the avian myelocytic leukemia retroviral v-myc gene, the ortholog of cellular c-myc, could be successfully used to immortalize human neural precursor cells [13; 14; 19].…”

Section: Discussionmentioning

confidence: 99%

“…Several lines of evidence indicate that transcription factors, such as Myc family members and their target genes, could be importantly involved in the maintenance of "stemness" of cells. It has been described that Myc-dependent mechanisms are involved in the control of the pluripotentency and self-renewing capability of murine embryonic stem cells [16] and neural progenitor cells [17; 18]. Several human NSC lines have been produced from whole human fetal brain or telecephalic region using the DNA sequence of the v-myc gene isolated from the avian myelocytic leukemia virus [13; 14; 19].…”

Section: Introductionmentioning

confidence: 99%

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Generation of human cortical neurons from a new immortal fetal neural stem cell line

Cacci

Villa

Parmar

et al. 2007

Experimental Cell Research

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Isolation and expansion of neural stem cells (NSCs) of human origin are crucial for successful development of cell therapy approaches in neurodegenerative diseases. Different epigenetic and genetic immortalization strategies have been established for long-term maintenance and expansion of these cells in vitro. Here we report the generation of a new, clonal NSC (hc-NSC) line, derived from human fetal cortical tissue, based on v-myc immortalization. Using immunocytochemistry, we show that these cells retain the characteristics of NSCs after more than 50 passages. Under proliferation conditions, when supplemented with epidermal and basic fibroblast growth factors, the hc-NSCs expressed neural stem/progenitor cell markers like nestin, vimentin and Sox2. When growth factors were withdrawn, proliferation and expression of v-myc and telomerase were dramatically reduced, and the hc-NSCs differentiated into glia. and neurons (mostly glutamatergic and GABAergic, as well as tyrosine hydroxylase-positive, presumably dopaminergic neurons). RT-PCR analysis showed that the hc-NSCs retained expression of Pax6, Emx2 and Neurogenin2, which are genes associated with regionalization and cell commitment in cortical precursors during brain development. Our data indicate that this hc-NSC line could be useful for exploring the potential of human NSCs to replace dead or damaged cortical cells in animal models of acute and chronic neurodegenerative diseases. Taking advantage of its clonality and homogeneity, this cell line will also be a valuable experimental tool to study the regulatory role of intrinsic and extrinsic factors in human NSC biology. (c) 2006 Elsevier Inc. All rights reserved

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Generation of human cortical neurons from a new immortal fetal neural stem cell line

Cacci

Villa

Parmar

et al. 2007

Experimental Cell Research

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“…In addition, LIF withdrawal results in the phosphorylation of MYC protein, mediated by GSK3B, which targets it for degradation. 11,13 Confirming its role as a self-renewal factor, MYC was shown to be able to maintain the ESC state in the absence of LIF when a non-degradable form was overexpressed following LIF withdrawal. 13 A stabilized form of MYC is one of only a small number of proteins that have been demonstrated to be able to maintain mouse ESC self-renewal in the absence of LIF.…”

Section: A Role For Polyamine Regulators In Esc Self-renewalmentioning

confidence: 93%

“…In this study, AMD1 was shown to promote high levels of MYC, which is an established self-renewal factor and previously demonstrated target of the polyamine pathway. 13,18,19 This was the first demonstration of a role for the polyamine pathway in the regulation of ESC self-renewal.…”

Section: A Role For Polyamine Regulators In Esc Self-renewalmentioning

confidence: 99%

A role for polyamine regulators in ESC self-renewal

Zhao

Goh

et al. 2012

Cell Cycle

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E mbryonic stem cells (ESCs) dependon extensive regulatory networks to coordinate their self-renewal and differentiation. The polyamine pathway regulator AMD1 was recently implicated in ESC self-renewal and directed differentiation of ESCs to neural precursor cells (NPCs). The polyamines spermine and spermidine are essential for a wide range of biological processes, and their levels are tightly regulated. Here, we review the polyamine pathway and discuss how it can impact polyamine levels, cellular methylation and hypusinated EIF5A levels. We discuss how it could feed into regulation of ESC self-renewal and directed differentiation. We show that in addition to AMD1, a second rate-limiting enzyme in the polyamine pathway, ODC1, can also promote ESC self-renewal, and that both Amd1 and Odc1 can partially substitute for Myc during cellular reprogramming. We propose that both Amd1 and Odc1 are essential regulators of ESCs and function to ensure high polyamine levels to promote ESC self-renewal.

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“…However, the importance of c-Myc transduction for iPSC generation has been suggested previously by genome-wide chromatin immunoprecipitation experiments [5], and the involvement of c-Myc in the pluripotency-maintenance machinery in embryonic stem (ES) cells has also been reported [6][7][8][9][10][11]. To date, substantial numbers of genes including noncoding transcripts have been identified as c-Myc-regulated genes [9,12].…”

Section: Introductionmentioning

confidence: 95%

Crucial Role of C-Myc in the Generation of Induced Pluripotent Stem Cells

Araki

Hoki²,

Uda³

et al. 2011

Stem Cells

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c-Myc transduction has been considered previously to be nonessential for induced pluripotent stem cell (iPSC) generation. In this study, we investigated the effects of c-Myc transduction on the generation of iPSCs from an inbred mouse strain using a genome integration-free vector to exclude the effects of the genetic background and the genomic integration of exogenous genes. Our findings reveal a clear difference between iPSCs generated using the four defined factors including c-Myc (4F-iPSCs) and those produced without cMyc (3F-iPSCs). Molecular and cellular analyses did not reveal any differences between 3F-iPSCs and 4F-iPSCs, as reported previously. However, a chimeric mice formation test indicated clear differences, whereby few highly chimeric mice and no germline transmission was observed using 3F-iPSCs. Similar differences were also observed in the mouse line that has been widely used in iPSC studies. Furthermore, the defect in 3F-iPSCs was considerably improved by trichostatin A, a histone deacetyl transferase inhibitor, indicating that c-Myc plays a crucial role in iPSC generation through the control of histone acetylation. Indeed, low levels of histone acetylation were observed in 3F-iPSCs. Our results shed new light on iPSC generation mechanisms and strongly recommend c-Myc transduction for preparing highquality iPSCs.

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LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism

Cited by 667 publications

References 51 publications

Generation of human cortical neurons from a new immortal fetal neural stem cell line

Generation of human cortical neurons from a new immortal fetal neural stem cell line

A role for polyamine regulators in ESC self-renewal

Crucial Role of C-Myc in the Generation of Induced Pluripotent Stem Cells

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