Chromatin-mediated translational control is essential for neural cell fate specification

Hwang, Dong-Woo; Jaganathan, Anbalagan; Shrestha, Padmina; Jin, Ying; El-Amine, Nour; Wang, Sidney H.; Hammell, Molly; Mills, Alea A.

doi:10.26508/lsa.201700016

Cited by 9 publications

(6 citation statements)

References 45 publications

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“…Our studies recapitulated this observation in GFAP expression during infection and in the long‐term survivors, consistent with sustained neuroinflammation. In NSCs, nestin expression increases during a shift from quiescence to activation (Hwang et al, 2018), suggesting that NSCs in the infected brain may be mobilized to replace lost NSCs or neurons. Even though nestin + cells decreased, we did not detect differences in total nestin expression in the brain tissue.…”

Section: Discussionmentioning

confidence: 99%

Perturbations in neural stem cell function during a neurotropic viral infection in juvenile mice

Kamte,

Chandwani,

London

et al. 2023

Journal of Neurochemistry

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Viral infections of the central nervous system (CNS) often cause worse neurological outcomes in younger hosts. Throughout childhood, the brain undergoes extensive development and refinement to produce functional neural networks. Network function is maintained partly with the help of neural stem cells (NSCs) that replace neuronal and glia subtypes in the two neurogenic niches of the brain (the hippocampus and subventricular zone). Accumulating evidence suggests that viruses disrupt NSC function in adulthood and infancy, but the in vivo impact of childhood infections on acute and long‐term NSC function is unknown. Using a juvenile mouse model of measles virus (MeV) infection, where only mature neurons in the brain are infected, we defined the effects of the antiviral immune response on NSCs from juvenile to adult stages of life. We found that (a) virus persists in the brains of survivors despite an anti‐viral immune response; (b) NSC numbers decrease dramatically during early infection, but ultimately stabilize in adult survivors; (c) infection is associated with mild apoptosis throughout the juvenile brain, but NSC proliferation is unchanged; (d) the loss of NSC numbers is dependent upon the stage of NSC differentiation; and (e) immature neurons increase early during infection, concurrent with depletion of NSC pools. Collectively, we show that NSCs are exquisitely sensitive to the inflammatory microenvironment created during neuron‐restricted MeV infection in juveniles, responding with an early loss of NSCs but increased neurogenesis. These studies provide insight into potential cellular mechanisms associated with long‐term neurological deficits in survivors of childhood CNS infections.image

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Section: Discussionmentioning

confidence: 99%

Perturbations in neural stem cell function during a neurotropic viral infection in juvenile mice

Kamte,

Chandwani,

London

et al. 2023

Journal of Neurochemistry

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“…Upon Chd5 depletion, NSCs differentiation was directed toward the astrocytic rather than the neuronal lineage. Boosting of astrocyte differentiation was due to translation disruption of Mash1, a main pro-neural TF that is essential during early differentiation (Hwang et al, 2018 ). These results suggest a strong Chd5 involvement in the cell fate decision in both cortical and hippocampal NSC niches at an early stage of differentiation.…”

Section: Profiling Of Enscs In the Physiological Environmentmentioning

confidence: 99%

“…NSCs and neural progenitors coexist in the embryonic as well as neonatal and adult stages, hence unveiling the mechanism of differentiation since early stages might bring an enormous insight into the global characterization of neurogenesis 10.3389/fncel.2023.1125785 (Codega et al, 2014). A study assessing global gene expression by RNA-seq has shown the role of the chromatin remodelers Chd5 at an early stage of development (Hwang et al, 2018). Chd5, expressed in the post-mitotic neurons, in the neural progenitors of E14.5 rat cortical region, and hippocampal progenitor cells, plays a critical role during neurogenesis (Egan et al, 2013;Vestin and Mills, 2013;Nitarska et al, 2016).…”

Section: Prenatal Development: Focus On Corticogenesismentioning

confidence: 99%

Endogenous neural stem cells characterization using omics approaches: Current knowledge in health and disease

Murtaj

Butti

Martino

et al. 2023

Front. Cell. Neurosci.

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Neural stem cells (NSCs), an invaluable source of neuronal and glial progeny, have been widely interrogated in the last twenty years, mainly to understand their therapeutic potential. Most of the studies were performed with cells derived from pluripotent stem cells of either rodents or humans, and have mainly focused on their potential in regenerative medicine. High-throughput omics technologies, such as transcriptomics, epigenetics, proteomics, and metabolomics, which exploded in the past decade, represent a powerful tool to investigate the molecular mechanisms characterizing the heterogeneity of endogenous NSCs. The transition from bulk studies to single cell approaches brought significant insights by revealing complex system phenotypes, from the molecular to the organism level. Here, we will discuss the current literature that has been greatly enriched in the “omics era”, successfully exploring the nature and function of endogenous NSCs and the process of neurogenesis. Overall, the information obtained from omics studies of endogenous NSCs provides a sharper picture of NSCs function during neurodevelopment in healthy and in perturbed environments.

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“…neuronal differentiation. However, emerging studies have established the importance of post-transcriptional mechanisms in neuronal differentiation (Kraushar et al, 2014(Kraushar et al, , 2015Blair et al, 2017;Sugiyama et al, 2017;Hwang et al, 2018;Zahr et al, 2018;Mohammad et al, 2019;Tahmasebi et al, 2019). Multiple miRNAs have been shown to regulate distinct aspects of neuronal differentiation (Stappert et al, 2015).…”

Section: Neurogenesis and Differentiationmentioning

confidence: 99%

The Role of Dynamic miRISC During Neuronal Development

Nawalpuri

Ravindran

Muddashetty

2020

Front. Mol. Biosci.

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Activity-dependent protein synthesis plays an important role during neuronal development by fine-tuning the formation and function of neuronal circuits. Recent studies have shown that miRNAs are integral to this regulation because of their ability to control protein synthesis in a rapid, specific and potentially reversible manner. miRNA mediated regulation is a multistep process that involves inhibition of translation before degradation of targeted mRNA, which provides the possibility to store and reverse the inhibition at multiple stages. This flexibility is primarily thought to be derived from the composition of miRNA induced silencing complex (miRISC). AGO2 is likely the only obligatory component of miRISC, while multiple RBPs are shown to be associated with this core miRISC to form diverse miRISC complexes. The formation of these heterogeneous miRISC complexes is intricately regulated by various extracellular signals and cell-specific contexts. In this review, we discuss the composition of miRISC and its functions during neuronal development. Neurodevelopment is guided by both internal programs and external cues. Neuronal activity and external signals play an important role in the formation and refining of the neuronal network. miRISC composition and diversity have a critical role at distinct stages of neurodevelopment. Even though there is a good amount of literature available on the role of miRNAs mediated regulation of neuronal development, surprisingly the role of miRISC composition and its functional dynamics in neuronal development is not much discussed. In this article, we review the available literature on the heterogeneity of the neuronal miRISC composition and how this may influence translation regulation in the context of neuronal development.

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Chromatin-mediated translational control is essential for neural cell fate specification

Abstract: Chd5 loss links the up-regulation of ribosomal genes to enhanced translation, causing the untimely production of a master transcription factor that unleashes stem cells and alters cell fate.

Cited by 9 publications

References 45 publications

Perturbations in neural stem cell function during a neurotropic viral infection in juvenile mice

Perturbations in neural stem cell function during a neurotropic viral infection in juvenile mice

Endogenous neural stem cells characterization using omics approaches: Current knowledge in health and disease

The Role of Dynamic miRISC During Neuronal Development

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