Cell cycle and pluripotency: Convergence on octamer-binding transcription factor 4

She, Shiqi; Wei, Qucheng; Kang, Bo; Wang, Yingjie

doi:10.3892/mmr.2017.7489

Cited by 22 publications

(24 citation statements)

References 131 publications

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“…Moreover, DNA damage response pathways, which are activated in the G1 phase, are reduced or absent in both hESCs and mESCs [ 43 ]. Several negative regulators of cell cycle progression, including p53, p16/INK4A, p19/ARF and p21/Cip1, are expressed at low levels in ESCs, while DNA repair and replication regulators are expressed at high levels [ 6 , 43 ].…”

Section: Mirnas and Cell Cycle Regulation Of Stem Cellsmentioning

confidence: 99%

“…A reduced G1 phase and prolonged S phase in ESCs are the causes that make this difference. In addition, human ESCs (hESCs) spend only 3 h in the G1 phase, compared to human somatic cells that spend 10 h in this phase [ 6 ]. The difference in cell cycle duration between ESCs and somatic stem cells is remarkable, an explanation could be that somatic stem cells are predominantly in a quiescent state compared to the fast dividing ESCs.…”

Section: Introductionmentioning

confidence: 99%

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Cell Cycle Regulation of Stem Cells by MicroRNAs

Mens

Ghanbari

2018

Stem Cell Rev and Rep

169

114

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MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of gene expression. They are involved in the fine-tuning of fundamental biological processes such as proliferation, differentiation, survival and apoptosis in many cell types. Emerging evidence suggests that miRNAs regulate critical pathways involved in stem cell function. Several miRNAs have been suggested to target transcripts that directly or indirectly coordinate the cell cycle progression of stem cells. Moreover, previous studies have shown that altered expression levels of miRNAs can contribute to pathological conditions, such as cancer, due to the loss of cell cycle regulation. However, the precise mechanism underlying miRNA-mediated regulation of cell cycle in stem cells is still incompletely understood. In this review, we discuss current knowledge of miRNAs regulatory role in cell cycle progression of stem cells. We describe how specific miRNAs may control cell cycle associated molecules and checkpoints in embryonic, somatic and cancer stem cells. We further outline how these miRNAs could be regulated to influence cell cycle progression in stem cells as a potential clinical application.

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Section: Mirnas and Cell Cycle Regulation Of Stem Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cell Cycle Regulation of Stem Cells by MicroRNAs

Mens

Ghanbari

2018

Stem Cell Rev and Rep

169

114

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“…When pRB is dephosphorylated and active, OCT4 and SOX2 promoters are inhibited 82 ; thus, P-pRB may promote OCT4/SOX2 expression in SPN-A566V cells, which in turn induce NANOG 83 , 84 . OCT4 regulates the self-renewal and differentiation of embryonic stem cells, at the same time controlling the cell cycle by increasing CDKs/Cyclin levels during the G1 phase and by preventing pRB dephosphorylation by PP1 82 , 85 , 86 . However, further studies are needed to clarify if the PP1-SPN holoenzyme plays any role in the OCT4/pRB self-regulatory circuit.…”

Section: Discussionmentioning

confidence: 99%

Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells

Verdugo‐Sivianes¹,

Rojas²,

Muñoz-Galván³

et al. 2021

Theranostics

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Rationale: SPINOPHILIN (SPN, PPP1R9B) is an important tumor suppressor involved in the progression and malignancy of different tumors depending on its association with protein phosphatase 1 (PP1) and the ability of the PP1-SPN holoenzyme to dephosphorylate retinoblastoma (pRB). Methods: We performed a mutational analysis of SPN in human tumors, focusing on the region of interaction with PP1 and pRB. We explored the effect of the SPN-A566V mutation in an immortalized non-tumorigenic cell line of epithelial breast tissue, MCF10A, and in two different p53-mutated breast cancer cells lines, T47D and MDA-MB-468. Results: We characterized an oncogenic mutation of SPN found in human tumor samples, SPN-A566V, that affects both the SPN-PP1 interaction and its phosphatase activity. The SPN-A566V mutation does not affect the interaction of the PP1-SPN holoenzyme with pocket proteins pRB, p107 and p130, but it affects its ability to dephosphorylate them during G0/G1 and G1, indicating that the PP1-SPN holoenzyme regulates cell cycle progression. SPN-A566V also promoted stemness, establishing a connection between the cell cycle and stem cell biology via pocket proteins and PP1-SPN regulation. However, only cells with both SPN-A566V and mutant p53 have increased tumorigenic and stemness properties. Conclusions: SPN-A566V, or other equivalent mutations, could be late events that promote tumor progression by increasing the CSC pool and, eventually, the malignant behavior of the tumor.

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“…The effects of the tested chemicals on the cell cycle and osteogenic differentiation could also involve a role of the upregulated OCT4 gene, as revealed by qRT-PCR. OCT4 has been suggested to promote G1/S transition and reduce differentiation, while also controlling cell cycle regulators to ensure a proper duration of G2 for checking genome integrity and decreasing chromosomal mis-segregation [50,51]. The prolonged chemically-induced hypoxic response could therefore have helped the AT-MSCs adapt for maintaining their stemness as well as proliferative capacity.…”

Section: Discussionmentioning

confidence: 99%

Proangiogenic Hypoxia-Mimicking Agents Attenuate Osteogenic Potential of Adipose Stem/Stromal Cells

Abu-Shahba

Gebraad

Kaur

et al. 2020

Tissue Eng Regen Med

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BACKGROUND: Insufficient vascularization hampers bone tissue engineering strategies for reconstructing large bone defects. Delivery of prolyl-hydroxylase inhibitors (PHIs) is an interesting approach to upregulate vascular endothelial growth factor (VEGF) by mimicking hypoxic stabilization of hypoxia-inducible factor-1alpha (HIF-1a). This study assessed two PHIs: dimethyloxalylglycine (DMOG) and baicalein for their effects on human adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs). METHODS: Isolated AT-MSCs were characterized and treated with PHIs to assess the cellular proliferation response. Immunostaining and western-blots served to verify the HIF-1a stabilization response. The optimized concentrations for long-term treatment were tested for their effects on the cell cycle, apoptosis, cytokine secretion, and osteogenic differentiation of AT-MSCs. Gene expression levels were evaluated for alkaline phosphatase (ALPL), bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor A (VEGFA), secreted phosphoprotein 1 (SPP1), and collagen type I alpha 1 (COL1A1). In addition, stemness-related genes Kruppel-like factor 4 (KLF4), Nanog homeobox (NANOG), and octamer-binding transcription factor 4 (OCT4) were assessed. RESULTS: PHIs stabilized HIF-1a in a dose-dependent manner and showed evident dose-and time dependent antiproliferative effects. With doses maintaining proliferation, DMOG and baicalein diminished the effect of osteogenic induction on the expression of RUNX2, ALPL, and COL1A1, and suppressed the formation of mineralized matrix. Suppressed osteogenic response of AT-MSCs was accompanied by an upregulation of stemness-related genes. CONCLUSION: PHIs significantly reduced the osteogenic differentiation of AT-MSCs and rather upregulated stemnessrelated genes. PHIs proangiogenic potential should be weighed against their longterm direct inhibitory effects on the osteogenic differentiation of AT-MSCs. Keywords Dimethyloxalylglycine Á Baicalein Á Hypoxia-inducible factor-1alpha Á Adipose tissue-derived mesenchymal stem/stromal cells Á Osteogenesis Riitta Seppänen-Kaijansinkko and Bettina Mannerström contributed equally.

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Cell cycle and pluripotency: Convergence on octamer-binding transcription factor 4

Cited by 22 publications

References 131 publications

Cell Cycle Regulation of Stem Cells by MicroRNAs

Cell Cycle Regulation of Stem Cells by MicroRNAs

Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells

Proangiogenic Hypoxia-Mimicking Agents Attenuate Osteogenic Potential of Adipose Stem/Stromal Cells

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