Oxidative stress promotes exit from the stem cell state and spontaneous neuronal differentiation

Hu, Qidong; Khanna, Puja; Wong, Belinda Shu Ee; Heng, Zealyn Shi Lin; Subhramanyam, Charannya Sozheesvari; Thanga, Lal Zo; Tan, Si Heng Sharon; Baeg, Gyeong Hun

doi:10.18632/oncotarget.23786

Cited by 51 publications

(48 citation statements)

References 52 publications

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“…To investigate whether extranuclear NANOG colocalizes with centrosomes, we performed double indirect immunofluorescence using an anti-pericentrin antibody specific for the detection of centrosomes ( Figure 2) combined with each of the two independent anti-NANOG commercial antibodies (Figure 3a-c). In addition to rhabdomyosarcoma cell lines, we also examined established and patient-derived tumor cell lines of neurogenic origin, as well as the NTERA-2 human pluripotent embryonal carcinoma cell line, which served as a positive control of nuclear NANOG expression [39]. Indeed, the localization of the fluorescence signal for NANOG colocalized with centrosomes in each of the nine examined tumor cell lines (Figure 3a-c).…”

Section: Centrosomal Localization Of the Nanog Proteinmentioning

confidence: 99%

NANOG/NANOGP8 Localizes at the Centrosome and is Spatiotemporally Associated with Centriole Maturation

Mikulenková

Neradil

Vymazal

et al. 2020

Cells

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NANOG is a transcription factor involved in the regulation of pluripotency and stemness. The functional paralog of NANOG, NANOGP8, differs from NANOG in only three amino acids and exhibits similar reprogramming activity. Given the transcriptional regulatory role played by NANOG, the nuclear localization of NANOG/NANOGP8 has primarily been considered to date. In this study, we investigated the intriguing extranuclear localization of NANOG and demonstrated that a substantial pool of NANOG/NANOGP8 is localized at the centrosome. Using double immunofluorescence, the colocalization of NANOG protein with pericentrin was identified by two independent anti-NANOG antibodies among 11 tumor and non-tumor cell lines. The validity of these observations was confirmed by transient expression of GFP-tagged NANOG, which also colocalized with pericentrin. Mass spectrometry of the anti-NANOG immunoprecipitated samples verified the antibody specificity and revealed the expression of both NANOG and NANOGP8, which was further confirmed by real-time PCR. Using cell fractionation, we show that a considerable amount of NANOG protein is present in the cytoplasm of RD and NTERA-2 cells. Importantly, cytoplasmic NANOG was unevenly distributed at the centrosome pair during the cell cycle and colocalized with the distal region of the mother centriole, and its presence was markedly associated with centriole maturation. Along with the finding that the centrosomal localization of NANOG/NANOGP8 was detected in various tumor and non-tumor cell types, these results provide the first evidence suggesting a common centrosome-specific role of NANOG.

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Section: Centrosomal Localization Of the Nanog Proteinmentioning

confidence: 99%

NANOG/NANOGP8 Localizes at the Centrosome and is Spatiotemporally Associated with Centriole Maturation

Mikulenková

Neradil

Vymazal

et al. 2020

Cells

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“…Higher concentrations of ROS (100 μM H 2 O 2 ) have been shown to increase the production of neuronal and oligodendroglial cells from neural precursor cells under differentiation conditions . Indeed, oxidative stress has been suggested to promote neuronal differentiation of NSPCs . Given the similarities between SVZ cells in the brain and spinal cord ependymal NSPCs, it is likely that many of the responses to ROS described within the brain also hold true for NSPCs in the spinal cord.…”

Section: Ros Regulates Nspc Proliferation Differentiation and Survivalmentioning

confidence: 99%

“…41 Indeed, oxidative stress has been suggested to promote neuronal differentiation of NSPCs. 42 Given the similarities between SVZ cells in the brain and spinal cord ependymal NSPCs, it is likely that many of the responses to ROS described within the brain also hold true for NSPCs in the spinal cord. However, only a small number of studies have specifically examined the effects of ROS on ependymal NSPCs to definitively confirm this postulate, and these studies showed that much higher levels of ROS (500 μM) are required to induce cell death in vitro compared with differentiated neurons.…”

Section: Nspcs Display a Unique Response To Ros Studies Conducted Onmentioning

confidence: 99%

Unlocking the paradoxical endogenous stem cell response after spinal cord injury

2019

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Nearly a century ago, the concept of the secondary injury in spinal cord trauma was first proposed to explain the complex cascade of molecular and cellular events leading to widespread neuronal and glial cell death after trauma. In recent years, it has been established that the ependymal region of the adult mammalian spinal cord contains a population of multipotent neural stem/progenitor cells (NSPCs) that are activated after spinal cord injury (SCI) and likely play a key role in endogenous repair and regeneration. How these cells respond to the various components of the secondary injury remains poorly understood. Emerging evidence suggests that many of the biochemical components of the secondary injury cascade which have classically been viewed as deleterious to host neuronal and glial cells may paradoxically trigger NSPC activation, proliferation, and differentiation thus challenging our current understanding of secondary injury mechanisms in SCI. Herein, we highlight new findings describing the response of endogenous NSPCs to spinal cord trauma, redefining the secondary mechanisms of SCI through the lens of the endogenous population of stem/progenitor cells. Moreover, we outline how these insights can fuel novel stem cell-based therapeutic strategies to repair the injured spinal cord. K E Y W O R D S ependymal cells, neural stem/progenitor cells, pathophysiology, spinal cord injury, secondary injury

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“…Moreover, mitochondrial ROS levels are crucial for the biological functions of stem cells (Zuluaga, Barzegari, Letourneur, Gueguen, & Pavon‐Djavid, 2017). Low levels of mitochondrial ROS production are demanded in some cellular processes such as proliferation and differentiation (Q. Hu, Khanna, et al, 2018; Pashkovskaia, Gey, & Rödel, 2018). It has been reported that the primary human mesenchymal stem cells (MSCs) may differentiate into adipocytes.…”

Section: Introductionmentioning

confidence: 99%

“…Low levels of mitochondrial ROS production are demanded in some cellular processes such as proliferation and differentiation (Q. Hu, Khanna, et al, 2018;Pashkovskaia, Gey, & Rödel, 2018). It has been reported that the primary human mesenchymal stem cells (MSCs) may differentiate into adipocytes.…”

mentioning

confidence: 99%

Mitochondria‐targeted antioxidant mito‐TEMPO alleviate oxidative stress induced by antimycin A in human mesenchymal stem cells

Nouri

Gueguen

Saeedi

et al. 2020

Journal Cellular Physiology

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The cell therapy of damaged tissue, which is linked to hypoxia condition might fail, in large part due to the emergence of oxidative stress (OS) and/or mitochondrial dysfunctions. Thus, the invigoration of stem cells against oxidative stress could be a reliable strategy to improve the cell therapy outcome. Of various antioxidants, mito‐Tempo (mito‐T) is one of the potent antioxidants that could target and neutralize the mitochondrial oxidative stress. In this study, for the induction of hypoxia and oxidative stress in mitochondria of the mesenchymal stem cells (MSCs) isolated from human adipose tissue, antimycin A (AMA) was used and then several parameters were analyzed, including cell viability and cell cycle arrest of MSCs exposed to AMA, mito‐T, antioxidant potential, redox homeostasis, and signaling pathways in MSCs under oxidative stress. Based on our findings, the treated MSCs were found to impose a high resistance to the OS‐induced apoptosis, which correlated with the nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway required to manage OS. Upon exposure of the MSCs to high oxidative stress conditions using AMA, the cells failed to scavenge. The use of mito‐T was found to alleviate the damage induced by oxidative stress through both direct functions of the free radical scavenging and the interplay in terms of cell signaling pathways including the upregulation of the Nrf2 pathway. These findings may pave the way in the stem cell therapy for the hypoxia‐mediated tissue damage.

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Oxidative stress promotes exit from the stem cell state and spontaneous neuronal differentiation

Cited by 51 publications

References 52 publications

NANOG/NANOGP8 Localizes at the Centrosome and is Spatiotemporally Associated with Centriole Maturation

NANOG/NANOGP8 Localizes at the Centrosome and is Spatiotemporally Associated with Centriole Maturation

Unlocking the paradoxical endogenous stem cell response after spinal cord injury

Mitochondria‐targeted antioxidant mito‐TEMPO alleviate oxidative stress induced by antimycin A in human mesenchymal stem cells

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