A role for polyamine regulators in ESC self-renewal

Zhao, Tianyun; Goh, Kim Jee; Ng, Huck Hui; Vardy, Leah A.

doi:10.4161/cc.22772

Cited by 32 publications

(33 citation statements)

References 49 publications

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“…Our results corroborate some of the previous studies reporting the oncogenic potential of edited AZIN1 in HCC and esophageal cancer (9,10). Additionally, ODC is known to promote self-renewal of embryonic stem cells via accumulation of polyamine (34). We showed that AZIN1 RNA editing levels are increased in spheroid-derived cancer stem-like cells and edited AZIN1 significantly enhanced spheroid formation, with a corresponding increase in stemness markers.…”

Section: Test) (B)supporting

confidence: 81%

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer

Shigeyasu¹,

Okugawa²,

Toden³

et al. 2018

JCI Insight

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Section: Test) (B)supporting

confidence: 81%

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer

Shigeyasu¹,

Okugawa²,

Toden³

et al. 2018

JCI Insight

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“…This downregulation is required for differentiation and high levels of AMD1 can drive self-renewal in the absence of the usually essential cytokine LIF. We have shown that AMD1 works in part through promotion of MYC protein stability, which is critical for self-renewal [8,9]. Here, we identify a new downstream target of the polyamines in mouse embryonic stem cells: MINDY1.…”

Section: Introductionmentioning

confidence: 92%

MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal

et al. 2018

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Embryonic stem cells have the ability to self-renew or differentiate and these processes are under tight control. We previously reported that the polyamine regulator AMD1 is critical for embryonic stem cell self-renewal. The polyamines putrescine, spermidine, and spermine are essential organic cations that play a role in a wide array of cellular processes. Here, we explore the essential role of the polyamines in the promotion of self-renewal and identify a new stem cell regulator that acts downstream of the polyamines: MINDY1. MINDY1 protein levels are high in embryonic stem cells (ESCs) and are dependent on high polyamine levels. Overexpression of MINDY1 can promote ESC self-renewal in the absence of the usually essential cytokine Leukemia Inhibitory Factor (LIF). MINDY1 protein is prenylated and this modification is required for its ability to promote self-renewal. We go on to show that Mindy1 RNA is targeted for repression by mir-710 during Neural Precursor cell differentiation. Taken together, these data demonstrate that high polyamine levels are required for ESC self-renewal and that they function, in part, through promotion of high MINDY1 levels. STEM CELLS 2018; 00:000-000 SIGNIFICANCE STATEMENTThis article shows that the polyamines, putrescine, spermidine, and spermine are essential for the maintenance of embryonic stem cell self-renewal. Inhibition of polyamine synthesis causes differentiation. This study identifies the MINDY1 protein as being a critical downstream target of the polyamines in driving self-renewal. MINDY1 functions to remove ubiquitin from target proteins this preventing their degradation. This study proposes that MINDY1 is a new critical regulator of stem cell self-renewal that functions to promote the stability of core self-renewal proteins.

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“…Although polyamines have pleiotropic actions in cellular systems, few molecular targets have been defined (Zhao et al, 2012). The mechanisms by which their absence or paucity induces or maintains diapause remain to be determined, but, given the developmental arrest of diapause, regulation of cell proliferation is an obvious candidate.…”

Section: The Uterus Dictates Diapausementioning

confidence: 99%

“…Furthermore, dormant blastocysts from both the wallaby and the mink do not reactivate when cultured in vitro (Moreau et al, 1995;Renfree and Shaw, 2000). One potential candidate for a missing factor is LIF, which is essential for embryonic stem cell proliferation (Zhao et al, 2012) and for implantation in the mouse (Hondo and Stewart, 2005). LIF expression in the uterine epithelium and glands appears at the termination of diapause in the mouse, mink and the wallaby (Bhatt et al, 1991;Stewart et al, 1992;Song et al, 1998;Renfree, personal communication).…”

Section: The Uterus Dictates Diapausementioning

confidence: 99%

Embryonic diapause: development on hold

Fenelon

Banerjee²,

Murphy³

2014

Int. J. Dev. Biol.

111

130

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Embryonic diapause, the temporary suspension of development of the embryo, is a fascinating reproductive strategy that has been frequently exploited across the animal kingdom. It is characterized by an arrest in development that occurs at the blastocyst stage in over 130 species of mammals. Its presumed function is to uncouple mating from parturition, to ensure that both occur at the most propitious moment for survival of the species. Diapause can be facultative, i.e. induced by physiological conditions, or obligate, i.e. present in every gestation of a species. In the latter case, the proximal signals for regulation are related to photoperiod. Three diverse models, the mouse, the mustelid carnivores and the wallaby have been studied in detail. From these studies it can be discerned that, although the endocrine cues responsible for induction of diapause and re-initiation of development vary widely between species, there are a number of commonalities. Evidence to date indicates that the uterus exercises the proximal regulatory influence over whether an embryo enters into and when it exits from diapause. Some factors have been identified that appear crucial to this regulation, in particular, the polyamines. Recent studies indicate that diapause can be induced in species where it does not exist in nature. This suggests that the potential for diapause in mammals to be due to a single evolutionary event, to which control mechanisms adapted when the trait was beneficial to reproductive success. Further work at the molecular, cellular and organismic levels will be required before the physiological basis of diapause is resolved.

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A role for polyamine regulators in ESC self-renewal

Cited by 32 publications

References 49 publications

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer

AZIN1 RNA editing confers cancer stemness and enhances oncogenic potential in colorectal cancer

MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal

Embryonic diapause: development on hold

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