Mammalian Cell Dedifferentiation as a Possible Outcome of Stress

Shoshani, Ofer; Zipori, Dov

doi:10.1007/s12015-011-9231-0

Cited by 25 publications

(18 citation statements)

References 47 publications

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“…4) is surprising. In an attempt to reconcile our findings with the vast literature on the role of CIN in cancer, we propose a modification of the current view: As culture conditions may impose stress on primary cells, it is hypothesized that polyploidization is one possible response, out of many (44)(45)(46)(47), to environmental insults. We propose a putative function of polyploidy in counteracting malignancy under environmental stress, such as that imposed on the liver cell population in vivo or on cells in ex vivo culture (Fig.…”

Section: Discussionmentioning

confidence: 79%

Polyploidization of Murine Mesenchymal Cells Is Associated with Suppression of the Long Noncoding RNA H19 and Reduced Tumorigenicity

et al. 2012

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Mesenchymal stromal cells (MSC) are used extensively in clinical trials; however, the possibility that MSCs have a potential for malignant transformation was raised. We examined the genomic stability versus the tumorforming capacity of multiple mouse MSCs. Murine MSCs have been shown to be less stable and more prone to malignant transformation than their human counterparts. A large series of independently isolated MSC populations exhibited low tumorigenic potential under syngeneic conditions, which increased in immunocompromised animals. Unexpectedly, higher ploidy correlated with reduced tumor-forming capacity. Furthermore, in both cultured MSCs and primary hepatocytes, polyploidization was associated with a dramatic decrease in the expression of the long noncoding RNA H19. Direct knockdown of H19 expression in diploid cells resulted in acquisition of polyploid cell traits. Moreover, artificial tetraploidization of diploid cancer cells led to a reduction of H19 levels, as well as to an attenuation of the tumorigenic potential. Polyploidy might therefore serve as a protective mechanism aimed at reducing malignant transformation through the involvement of the H19 regulatory long noncoding RNA. Cancer Res; 72(24); 6403-13. Ó2012 AACR.

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Section: Discussionmentioning

confidence: 79%

Polyploidization of Murine Mesenchymal Cells Is Associated with Suppression of the Long Noncoding RNA H19 and Reduced Tumorigenicity

et al. 2012

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“…The effect of stress on cell reprogramming was previously predicted [77]. The various studies described above all point to the possibility that stress plays an important role in defining cell fate.…”

Section: Outcomes Of Stress In Mammalian Cellsmentioning

confidence: 82%

Stress as a fundamental theme in cell plasticity

Shoshani

Zipori

2015

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…Indeed, molecular, biochemical, and bioinformatic analyses suggest that Arabidopsis plants responding to various stress conditions feature dedifferentiation and acquisition of stem cell-like state prior to a switch in cell fate (Grafi et al, 2011a, and references therein). Likewise, it has recently been proposed that cell dedifferentiation may occur in mammalian somatic cells as an adaptation for extreme stress conditions (Shoshani and Zipori, 2011). …”

Section: Switching Cell Fate In Plantsmentioning

confidence: 99%

The Stem Cell State in Plant Development and in Response to Stress

Grafi¹,

Florentin²,

Ransbotyn³

et al. 2011

Front. Plant Sci.

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Stem cells are commonly defined by their developmental capabilities, namely, self-renewal and multitype differentiation, yet the biology of stem cells and their inherent features both in plants and animals are only beginning to be elucidated. In this review article we highlight the stem cell state in plants with reference to animals and the plastic nature of plant somatic cells often referred to as totipotency as well as the essence of cellular dedifferentiation. Based on recent published data, we illustrate the picture of stem cells with emphasis on their open chromatin conformation. We discuss the process of dedifferentiation and highlight its transient nature, its distinction from re-entry into the cell cycle and its activation following exposure to stress. We also discuss the potential hazard that can be brought about by stress-induced dedifferentiation and its major impact on the genome, which can undergo stochastic, abnormal reorganization leading to genetic variation by means of DNA transposition and/or DNA recombination.

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Mammalian Cell Dedifferentiation as a Possible Outcome of Stress

Cited by 25 publications

References 47 publications

Polyploidization of Murine Mesenchymal Cells Is Associated with Suppression of the Long Noncoding RNA H19 and Reduced Tumorigenicity

Polyploidization of Murine Mesenchymal Cells Is Associated with Suppression of the Long Noncoding RNA H19 and Reduced Tumorigenicity

Stress as a fundamental theme in cell plasticity

The Stem Cell State in Plant Development and in Response to Stress

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