PAX3 inhibits β-Tubulin-III expression and neuronal differentiation of neural stem cell

Cao, Sixian; Du, Jinfeng; Lv, Yan; Lin, Hengrong; Mao, Zuming; Xu, Man; Liu, Yan

doi:10.1016/j.bbrc.2017.02.086

Cited by 15 publications

(19 citation statements)

References 20 publications

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“…Cells isolated from the human olfactory mucosa of controls and FRDA patients were positive for Nanog, an embryonic stem cell marker [ 47 ] and Klf4, a pluripotent stem cell marker [ 48 ]. The samples also expressed Sox9, an early neural crest derived marker [ 49 ], Sox2, required for stem-cell maintenance in the central nervous system [ 50 ] and Pax3, involved in neural development [ 51 ]. In addition, mucosa-derived cells expressed TrkB, a receptor of the neurotrophin BDNF able to mediate proliferation and differentiation of neuronal cells [ 52 ] and PTCH1, a transmembrane receptor in the Sonic-Hedgehog pathway, also found to be expressed in embryonic stem cells [ 53 ].…”

Section: Resultsmentioning

confidence: 99%

Altered Secretome and ROS Production in Olfactory Mucosa Stem Cells Derived from Friedreich’s Ataxia Patients

Pérez-Luz

Loría

Katsu-Jiménez

et al. 2020

IJMS

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Friedreich’s ataxia is the most common hereditary ataxia for which there is no cure or approved treatment at present. However, therapeutic developments based on the understanding of pathological mechanisms underlying the disease have advanced considerably, with the implementation of cellular models that mimic the disease playing a crucial role. Human olfactory ecto-mesenchymal stem cells represent a novel model that could prove useful due to their accessibility and neurogenic capacity. Here, we isolated and cultured these stem cells from Friedreich´s ataxia patients and healthy donors, characterizing their phenotype and describing disease-specific features such as reduced cell viability, impaired aconitase activity, increased ROS production and the release of cytokines involved in neuroinflammation. Importantly, we observed a positive effect on patient-derived cells, when frataxin levels were restored, confirming the utility of this in vitro model to study the disease. This model will improve our understanding of Friedreich´s ataxia pathogenesis and will help in developing rationally designed therapeutic strategies.

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Section: Resultsmentioning

confidence: 99%

Altered Secretome and ROS Production in Olfactory Mucosa Stem Cells Derived from Friedreich’s Ataxia Patients

Pérez-Luz

Loría

Katsu-Jiménez

et al. 2020

IJMS

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“…Despite the current emphasis on the significance of posttranslational tubulin modifications in the central nervous system, tubulin acetylation and polyglutamylation patterns during the differentiation of neural stem cells have not been thoroughly explored (Cao et al, 2017; Sheikh et al 2021). The expression of βIII-tubulin in neurons is well documented (Kapitein and Hoogenraad, 2015; Moody et al, 1989; Lee et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Post-Translational Tubulin Modifications in Differentiated Human Neural Stem Cells

Knight

Jogalekar

Serrano

2022

Preprint

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The tubulin protein fulfills a variety of cellular functions that range from chromosomal separation to locomotion. The functional diversity of tubulin is achieved through the expression of specific tubulin isotypes in different cell types or developmental time periods. Post-translational modifications (PTMs) of tubulin also are vital for specific intracellular tasks, such as binding and recruiting motor proteins. In neurons, the isotypic expression profile for tubulin is well characterized, and the importance of PTMs for proper neuronal function has gained recent attention due to their implication in neurodegenerative disorders. In contrast, the role of tubulin specializations in the specification of neural cell fate has received minimal attention and studies of tubulin PTMs and isotypes in neuroglia such as astrocytes are relatively few. To bridge this knowledge gap, we undertook an analysis of PTMs in neurons and astrocytes derived from the federally approved H9 hESC-derived human neural stem cell (hNSC) line. In hNSCs, basal cells can be directed to assume neural fate as neurons or astrocytes by specifying different media growth conditions. Immunocytochemical methods, fluorescent antibody probes, and confocal microscopy facilitated image acquisition of fluorescent signals from class III β- tubulin (βIII-tubulin), acetylated tubulin, and polyglutamylated tubulin. Fluorescent probe intensities were assessed with the EBImage package for the statistical programming language R and compared using Student's t-tests. Qualitative analysis indicated that βIII-tubulin, acetylated tubulin, and polyglutamylated tubulin were expressed to some degree in basal hNSCs and their media-differentiated hNSC neuronal and astroglial progeny. In media-differentiated hNSC astrocyte progeny, quantification and statistical analysis of fluorescence probe intensity showed that acetylated tubulin/ βIII-tubulin ratios were greater than the ratio for polyglutamylated tubulin/ βIII-tubulin. These findings represent a snapshot of the dynamic and varied changes tubulin expression profile during the specification of neural cell fate. Results imply that investigations of tubulin PTMs have the potential to advance our understanding of the generation and regeneration of nervous tissue.

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“…Expression of neuronal markers was assessed by Western blot in differentiating NG108-15 cells, following exposure to SCs at the conditions that previously enhanced differentiation, that is, single exposure to THJ-2201 or repeated exposure to 5F-PB22. Four specific proteins were analyzed: β3tubulin, a cytoskeleton protein mostly expressed in immature neurons [24]; synaptophysin, a synaptic vesicle protein that regulates vesicle endocytosis in neurons [25]; post-synaptic density protein 95 (PSD-95), a synaptic protein involved in the maturation of excitatory synapses [26]; and p73, which induces the expression of neurofilaments and neural cell adhesion molecule (N-CAM) [27,28]. Figure 7 shows that 5F-PB22 significantly increased the expression of β3-tubulin and PSD-95 at 1 nM ( Figure 7A and C, respectively), and of p73 at 1 pM ( Figure 7D), compared to these markers' expression in vehicle-treated cells.…”

Section: Expression Of Neuronal Markersmentioning

confidence: 99%

The Synthetic Cannabinoids THJ-2201 and 5F-PB22 Enhance In Vitro CB1 Receptor-Mediated Neuronal Differentiation at Biologically Relevant Concentrations

Alexandre

Malheiro

Silva

et al. 2020

IJMS

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Recreational use of synthetic cannabinoids (SCs) before and during pregnancy poses a major public health risk, due to the potential onset of neurodevelopmental disorders in the offspring. Herein, we report the assessment of the neurotoxic potential of two commonly abused SCs, THJ-2201 and 5F-PB22, particularly focusing on how they affect neuronal differentiation in vitro. Differentiation ratios, total neurite length, and neuronal marker expression were assessed in NG108-15 neuroblastoma x glioma cells exposed to the SCs at non-toxic, biologically relevant concentrations (≤1 μM), either in acute or repeated exposure settings. Both SCs enhanced differentiation ratios and total neurite length of NG108-15 cells near two-fold compared to vehicle-treated cells, in a CB1R activation-dependent way, as the CB1R blockade with a specific antagonist (SR141718) abrogated SC-induced effects. Interestingly, repeated 5F-PB22 exposure was required to reach effects similar to a single THJ-2201 dose. Cell viability and proliferation, mitochondrial membrane potential, and intracellular ATP levels were also determined. The tested SCs increased mitochondrial tetramethyl rhodamine ethyl ester (TMRE) accumulation after 24 h at biologically relevant concentrations but did not affect any of the other toxicological parameters. Overall, we report firsthand the CB1R-mediated enhancement of neurodifferentiation by 5F-PB22 and THJ-2201 at biologically relevant concentrations.

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PAX3 inhibits β-Tubulin-III expression and neuronal differentiation of neural stem cell

Cited by 15 publications

References 20 publications

Altered Secretome and ROS Production in Olfactory Mucosa Stem Cells Derived from Friedreich’s Ataxia Patients

Altered Secretome and ROS Production in Olfactory Mucosa Stem Cells Derived from Friedreich’s Ataxia Patients

Post-Translational Tubulin Modifications in Differentiated Human Neural Stem Cells

The Synthetic Cannabinoids THJ-2201 and 5F-PB22 Enhance In Vitro CB1 Receptor-Mediated Neuronal Differentiation at Biologically Relevant Concentrations

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