myc maintains embryonic stem cell pluripotency and self-renewal

Varlakhanova, Natalia V.; Cotterman, Rebecca; deVries, Wilhelmine N.; Morgan, Janet; Donahue, Leah Rae; Murray, Stephen A.; Knowles, Barbara B.; Knoepfler, Paul S.

doi:10.1016/j.diff.2010.05.001

Cited by 170 publications

(157 citation statements)

References 59 publications

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“…As a key factor in reprogramming, Klf4 functions as a transcriptional activator and repressor to regulate the proliferation and differentiation of different cell types (35). c-Myc induces DNA replication and cell cycle progression, and modulates the ESC epigenome, promoting the opening of chromatin to allow the access of pluripotent factors (36,37). In the current study, gene expression patterns of AT-MSCs derived from three donors were investigated.…”

Section: Discussionmentioning

confidence: 98%

Cell culture density affects the stemness gene expression of adipose tissue-derived mesenchymal stem cells

Kim

Lee

et al. 2017

Biomedical Reports

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Abstract.The results of clinical trials using mesenchymal stem cells (MSCs) are controversial due to the heterogeneity of human MSCs and differences in culture conditions. In this regard, it is important to identify gene expression patterns according to culture conditions, and to determine how the cells are expanded and when they should be clinically used. In the current study, stemness gene expression was investigated in adipose tissue-derived MSCs (AT-MSCs) harvested following culture at different densities. AT-MSCs were plated at a density of 200 or 5,000 cells/cm 2 . After 7 days of culture, stemness gene expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The proliferation rate of AT-MSCs harvested at a low density (~50% confluent) was higher than that of AT-MSCs harvested at a high density (~90% confluent). Although there were differences in the expression levels of stemness gene, such as octamer-binding transcription factor 4, nanog homeobox (Nanog), SRY-box 2, Kruppel like factor 4, v-myc avian myelocytomatosis viral oncogene homolog (c-Myc), and lin-28 homolog A, in the AT-MSCs obtained from different donors, RT-qPCR analysis demonstrated differential gene expression patterns according to the cell culture density. Expression levels of stemness genes, particularly Nanog and c-Myc, were upregulated in AT-MSCs harvested at a low density (~50% confluent) in comparison to AT-MSCs from the same donor harvested at a high density (~90% confluent).These results imply that culture conditions, such as the cell density at harvesting, modulate the stemness gene expression and proliferation of MSCs.

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Section: Discussionmentioning

confidence: 98%

Cell culture density affects the stemness gene expression of adipose tissue-derived mesenchymal stem cells

Kim

Lee

et al. 2017

Biomedical Reports

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“…NT5E was only observed by passage 2 and ENG was not expressed at all. More importantly, cultured AF-MSCs expressed pluripotency markers such as the Octamer binding protein 3/4 (OCT3/4) and MYC (Pan et al 2002, Tsai et al 2004, Bossolasco et al 2006, De Coppi et al 2007, Roubelakis et al 2007, which are known to maintain stem cell pluripotency and selfrenewal (Varlakhanova et al 2010). Similarly, AECs were positive for CD44, ITGB1, NT5E, ENG, ALCAM, and MHC-I and negative for CD34, CD14, PTPRC, and MHC-II expression (Miki et al 2007b, Soncini et al 2007, Manuelpillai et al 2011.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cells from amnion and amniotic fluid in the bovine

Corradetti¹,

Meucci²,

Bizzaro³

et al. 2013

Reproduction

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Amnion and amniotic fluid (AF) are noncontroversial and inexhaustible sources of mesenchymal stem cells (MSCs) that can be harvested noninvasively at low cost. As in humans, also in veterinary field, presumptive stem cells derived from these tissues reveal as promising candidates for disease treatment, specifically for their plasticity, their reduced immunogenicity, and high anti-inflammatory potential. The aim of this work is to obtain and characterize, for the first time in bovine species, presumptive MSCs from the epithelial portion of the amnion (AECs) and from the AF (AF-MSCs) to be used for clinical applications. AECs display a polygonal morphology, whereas AF-MSCs exhibit a fibroblastic-like morphology only starting from the second passage, being heterogeneous during the primary culture. For both lines, the proliferative ability has been found constant over the ten passages studied and AECs show a statistically lower (P!0.05) doubling time with respect to AF-MSCs. AECs express MSC-specific markers (ITGB1 (CD29), CD44, ALCAM (CD166), ENG (CD105), and NT5E (CD73)) from P1 to P3; in AF-MSCs, only ITGB1, CD44, and ALCAM mRNAs are detected; NT5E is expressed from P2 and ENG has not been found at any passage. AF-MSCs and AECs are positive for the pluripotent markers (POU5F1 (OCT4) and MYC (c-Myc)) and lack of the hematopoietic markers. When appropriately induced, both cell lines are capable of differentiating into ectodermal and mesodermal lineages. This study contributes to reinforce the emerging importance of these cells as ideal tools in veterinary medicine. A deeper evaluation of the immunological properties needs to be performed in order to better understand their role in cellular therapy.

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“…Embryonic stem cells (ESCs) isolated from mice lacking either MYC or MYCN are capable of long-term self-renewal and remain pluripotent (Malynn et al 2000), consistent with other studies showing that MYC performs redundant roles in peri-implantation development. Simultaneous deletion of floxed MYC and MYCN alleles, however, destabilize the pluripotent state resulting in differentiation toward endoderm and mesoderm (Smith et al 2010;Varlakhanova et al 2010). A similar phenomenon occurs in hematopoietic stem cells, in which loss of either MYC or MYCN expression is largely inconsequential, whereas deficiency of both is lethal .…”

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confidence: 93%

Roles for MYC in the Establishment and Maintenance of Pluripotency

Chappell

Dalton

2013

Cold Spring Harbor Perspectives in Medicine

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MYC and MYCN have been directly implicated in the transcriptional regulation of several thousand genes in pluripotent stem cells and possibly contribute to the activity of all transcribed genes. Control of transcription by a pause-release mechanism, recruitment of positive and negative epigenetic regulators, and a general role in transcriptional amplification have all been implicated as part of the broad, overarching mechanism by which MYC controls stem cell biology. As would be anticipated from the regulation of so many genes, MYC is involved in a wide range of cellular processes including cell-cycle control, metabolism, signal transduction, self-renewal, maintenance of pluripotency, and control of cell fate decisions. MYC transcription factors also have clear roles in cell reprogramming and establishment of the pluripotent state. The mechanism by which MYC accomplishes this is now being explored and promises to uncover unexpected facets of general MYC regulation that are likely to be applicable to cancer biology. In this work we review our current understanding of how MYC contributes to the maintenance and establishment of pluripotent cells and how it contributes to early embryonic development. W ell before MYC was implicated in the establishment and maintenance of pluripotency, it was known as a potent oncogene with roles in transcriptional regulation of metabolism, differentiation, cell lifespan, cell cycle, and cell size control. These functions are all generally relevant to the maintenance and establishment of pluripotent stem cells. Despite this, however, defining the precise mechanism by which MYC functions has been problematic and has led to much confusion. The following discussion will focus on our current understanding of how MYC functions in early embryonic development, maintenance of stem cell identity, and in somatic cell reprogramming. MYC AND MYCN ARE FUNCTIONALLY REDUNDANT IN EARLY EMBRYONIC DEVELOPMENTThe MYC family of basic helix-loop-helix leucine zipper transcription factors consists of MYC, MYCN, and MYCL. DNA binding of MYC family members usually requires heterodimerization with MAX (Myc-associated factor X) through their respective leucine zipper do-

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myc maintains embryonic stem cell pluripotency and self-renewal

Cited by 170 publications

References 59 publications

Cell culture density affects the stemness gene expression of adipose tissue-derived mesenchymal stem cells

Cell culture density affects the stemness gene expression of adipose tissue-derived mesenchymal stem cells

Mesenchymal stem cells from amnion and amniotic fluid in the bovine

Roles for MYC in the Establishment and Maintenance of Pluripotency

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