Embryonic stem‐like cells from rabbit blastocysts cultured with melatonin could differentiate into three germ layers in vitro and in vivo

Wei, Ruxue; Zhao, Xiao‐Fan; Huang, Hao; Du, Weihua; Zhu, Huabin

doi:10.1002/mrd.22739

Cited by 7 publications

(8 citation statements)

References 44 publications

(67 reference statements)

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“…We showed elevated levels of NANOG transcripts in GLC incubated with 10 nmol/L MEL, which is contrary to recent findings in ovarian cancer stem cells [9], but in line with other reports showing enhanced expression of c-Myc and Nanog after MEL treatment [24]. Up-regulation of NANOG expression by MEL in nontumour ovarian GLC as demonstrated in the present study points out at the balancing role of the circadian hormone in a physiological context depending on cell type, period of exposure and dose applied.…”

Section: Expression Of Klf4 Myc and Nanogsupporting

confidence: 79%

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Melatonin selectively influences the transcription of pluripotency and differentiation markers in human non-cancer cells

Georgiev

Marinova

Konakchieva

et al. 2019

Biotechnology & Biotechnological Equipment

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Melatonin (MEL) may influence the efficiency of reprogramming both by somatic cell nuclear transfer and by direct induction of pluripotent stem cells (iPSC) through a yet unidentified mechanism. Transcription factors linked to cell reprogramming and cell signalling may be differentially expressed according to cell differentiation status. To address the effect of MEL on the expression of transcription factors linked to reprogramming, we used two distinct in vitro models of cellular plasticity: human foreskin fibroblasts (HFF) and primary human granulosa-lutein cells (GLC). Realtime quantitative polymerase chain reaction (qRT-PCR) analysis revealed amplification of transcripts for KLF4, MYC and NANOG in both cell types. In GLC, treatment with 10 nmol/L of MEL provoked significant up-regulation of the expression of MYC and NANOG compared to controls. KLF4 expression was not altered in GLC but was significantly down-regulated in MEL-treated HFF cells. Alterations in the expression of ERK1/2 and pERK1/2 in GLC as analyzed by Western blot were not observed regardless of the MEL treatment. On the contrary, HFF cells responded to MEL treatment with 1.6-fold higher levels of pERK1/2 compared to the non-treated controls. Our data suggest that the activation of MT1 melatonin receptor is probably related to phosphorylation of ERK1/2 at least in expanding HFF, which subsequently may act to alter gene expression and regulate cell fate. In conclusion, we demonstrated for the first time, the selective effect of MEL in vitro at physiological concentration on transcription factors regulating pluripotency and differentiation in human non-cancer cells according to cell differentiation status.

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Section: Expression Of Klf4 Myc and Nanogsupporting

confidence: 79%

“…It is known that KLF4 mRNA levels are higher in quiescent fibroblasts and almost undetectable in cells during exponential growth [23]. Elevated levels of Klf4 after treatment with MEL has also been reported in embryonic stem-like cells from rabbit blastocysts [24].…”

Section: Expression Of Klf4 Myc and Nanogmentioning

confidence: 95%

Melatonin selectively influences the transcription of pluripotency and differentiation markers in human non-cancer cells

Georgiev

Marinova

Konakchieva

et al. 2019

Biotechnology & Biotechnological Equipment

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“…Notably, p‐STAT‐6 interacts with PPAR‐γ and KLF4 to activate target gene expression (eg, Arg1 ). Actually, melatonin facilitates the expression of KLF4 (Figure B) . Additionally, melatonin reduces MT 1/2 ‐dependently the phosphorylation of the PI3K p85 regulatory subunit, which interacts with downstream Akt/mTORC1 to diminish M2 polarization.…”

Section: Mechanisms Whereby Melatonin Regulates Macrophage Polarizationmentioning

confidence: 97%

“…Actually, melatonin facilitates the expression of KLF4 ( Figure 2B). 172 Additionally, melatonin reduces MT 1/2 -dependently the phosphorylation of the PI3K p85 regulatory subunit, 173 which interacts with downstream Akt/mTORC1 to diminish M2 polarization. Therefore, melatonin may maintain the M2 macrophages by inhibiting the PI3K-mTOR pathway ( Figure 2C).…”

Section: Melatonin Shapes Macrophage Polarization Through Cellular mentioning

confidence: 99%

Melatonin in macrophage biology: Current understanding and future perspectives

Xia

Chen

Zeng

et al. 2019

Journal of Pineal Research

152

126

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Melatonin is a ubiquitous hormone found in various organisms and highly affects the function of immune cells. In this review, we summarize the current understanding of the significance of melatonin in macrophage biology and the beneficial effects of melatonin in macrophage‐associated diseases. Enzymes associated with synthesis of melatonin, as well as membrane receptors for melatonin, are found in macrophages. Indeed, melatonin influences the phenotype polarization of macrophages. Mechanistically, the roles of melatonin in macrophages are related to several cellular signaling pathways, such as NF‐κB, STATs, and NLRP3/caspase‐1. Notably, miRNAs (eg, miR‐155/‐34a/‐23a), cellular metabolic pathways (eg, α‐KG, HIF‐1α, and ROS), and mitochondrial dynamics and mitophagy are also involved. Thus, melatonin modulates the development and progression of various macrophage‐associated diseases, such as cancer and rheumatoid arthritis. This review provides a better understanding about the importance of melatonin in macrophage biology and macrophage‐associated diseases.

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“…Thus, such cell cycle re-entry in primary neurons leads to tau phosphorylation and conformational changes, as observed in AD [ 26 ], as well as neuronal cell death, gliosis and cognitive deficits. In direct connexion with these events, while melatonin drives the circadian amplitudes of proliferation genes like c-Myc [ 265 , 266 ], it also reduces c-Myc expression [ 267 ] to potentially prevent AD-associated excessive cell cycle re-entry. From a mechanistic point of view, c-Myc levels are positively controlled by ERK, which phosphorylates and stabilizes c-Myc and thus allows it to act on growth and transformation genes promoters [ 268 ], with aberrant activation of MEK/ERK signalling, promoting the entry of neurons into the cell cycle and their apoptosis [ 134 ].…”

Section: Role Of Melatonin In Regulating the Cell Cycle During Neurog...mentioning

confidence: 99%

Melatonin as a Harmonizing Factor of Circadian Rhythms, Neuronal Cell Cycle and Neurogenesis: Additional Arguments for Its Therapeutic Use in Alzheimer’s Disease

Shukla

Vincent

2023

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The synthesis and release of melatonin in the brain harmonize various physiological functions. The apparent decline in melatonin levels with advanced aging is an aperture to the neurodegenerative processes. It has been indicated that down regulation of melatonin leads to alterations of circadian rhythm components, which further causes a desynchronization of several genes and results in an increased susceptibility to develop neurodegenerative diseases. Additionally, as circadian rhythms and memory are intertwined, such rhythmic disturbances influence memory formation and recall. Besides, cell cycle events exhibit a remarkable oscillatory system, which is downstream of the circadian phenomena. The linkage between the molecular machinery of the cell cycle and complex fundamental regulatory proteins emphasizes the conjectural regulatory role of cell cycle components in neurodegenerative disorders such as Alzheimer’s disease. Among the mechanisms intervening long before the signs of the disease appear, the disturbances of the circadian cycle, as well as the alteration of the machinery of the cell cycle and impaired neurogenesis, must hold our interest. Therefore, in the present review, we propose to discuss the underlying mechanisms of action of melatonin in regulating the circadian rhythm, cell cycle components and adult neurogenesis in the context of AD pathogenesis with the view that it might further assist to identify new therapeutic targets.

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Embryonic stem‐like cells from rabbit blastocysts cultured with melatonin could differentiate into three germ layers in vitro and in vivo

Cited by 7 publications

References 44 publications

Melatonin selectively influences the transcription of pluripotency and differentiation markers in human non-cancer cells

Melatonin selectively influences the transcription of pluripotency and differentiation markers in human non-cancer cells

Melatonin in macrophage biology: Current understanding and future perspectives

Melatonin as a Harmonizing Factor of Circadian Rhythms, Neuronal Cell Cycle and Neurogenesis: Additional Arguments for Its Therapeutic Use in Alzheimer’s Disease

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