Histone deacetylase inhibition promotes regenerative neurogenesis after stab wound injury in the adult zebrafish optic tectum

Kiyooka, Mariko; Shimizu, Yuki; Ohshima, Toshio

doi:10.1016/j.bbrc.2020.06.025

Cited by 12 publications

(10 citation statements)

References 29 publications

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“…82,83 HDACs may also regulate neurogenesis through changes in Notch target gene expression by histone deacetylation. 84 Furthermore, the HDAC inhibitor, VPA, leads to an activation of the Notch signaling cascade by inducing a γ-secretase dependent activation of Notch signaling, resulting in increased levels of NICD. 85 In our studies, there was a trend of enhanced histone acetylation while Notch signaling was significantly downregulated on the microgrooved substrates.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, HDAC/silencing mediator of retinoid and thyroid hormone receptors (SMRT) complexes have been shown to inhibit the Notch signaling pathway by repressing the transcription of its downstream genes, such as Hes1. , HDACs may also regulate neurogenesis through changes in Notch target gene expression by histone deacetylation . Furthermore, the HDAC inhibitor, VPA, leads to an activation of the Notch signaling cascade by inducing a γ-secretase dependent activation of Notch signaling, resulting in increased levels of NICD .…”

Section: Discussionmentioning

confidence: 99%

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Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates

Hsu

Serio

Gopal

et al. 2022

ACS Appl. Mater. Interfaces

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A number of studies have recently shown how surface topography can alter the behavior and differentiation patterns of different types of stem cells. Although the exact mechanisms and molecular pathways involved remain unclear, a consistent portion of the literature points to epigenetic changes induced by nuclear remodeling. In this study, we investigate the behavior of clinically relevant neural populations derived from human pluripotent stem cells when cultured on polydimethylsiloxane microgrooves (3 and 10 μm depth grooves) to investigate what mechanisms are responsible for their differentiation capacity and functional behavior. Our results show that microgrooves enhance cell alignment, modify nuclear geometry, and significantly increase cellular stiffness, which we were able to measure at high resolution with a combination of light and electron microscopy, scanning ion conductance microscopy (SICM), and atomic force microscopy (AFM) coupled with quantitative image analysis. The microgrooves promoted significant changes in the epigenetic landscape, as revealed by the expression of key histone modification markers. The main behavioral change of neural stem cells on microgrooves was an increase of neuronal differentiation under basal conditions on the microgrooves. Through measurements of cleaved Notch1 levels, we found that microgrooves downregulate Notch signaling. We in fact propose that microgroove topography affects the differentiation potential of neural stem cells by indirectly altering Notch signaling through geometric segregation and that this mechanism in parallel with topography-dependent epigenetic modulations acts in concert to enhance stem cell neuronal differentiation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates

Hsu

Serio

Gopal

et al. 2022

ACS Appl. Mater. Interfaces

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“…Previously, we found that RG proliferation was induced by stab wound injury in the adult optic tectum (Shimizu et al, 2018) while other studies have shown that immune responses during the early stages after stab wound injury are required for RG proliferation in the adult telencephalon and optic tectum (Kyritsis et al, 2012;Ueda et al, 2018). Although molecular pathways that work in RG after the tectum injury have been well investigated by pharmacological experiments, transgenic lines and single cell RNA-seq (Shimizu et al, 2018;Ueda et al, 2018;Lindsey et al, 2019;Yu and He, 2019;Kiyooka et al, 2020), the global changes in gene expression related to immune activation and RG proliferation during the early stages of optic tectum regeneration had not yet been investigated. In this study, we first determined the time points for RNAseq by evaluating RG and macrophage responses at 6, 12, and 24 hpi.…”

Section: Stab Wound Injury Induced Macrophage Migration and Rg Proliferation In The Adult Optic Tectum Within 24 Hmentioning

confidence: 99%

“…These findings suggest that stat3, ascl1a, lin28a, sox2, and her4 play important roles in RG activation during tectum regeneration. The regulation of adult and regenerative neurogenesis by her family genes and Notch signaling have been well studied in the optic tectum (Dozawa et al, 2014;Ueda et al, 2018;Yu and He, 2019;Kiyooka et al, 2020); however, further studies are required to investigate the regulation of adult NSCs by ascl1a, lin28a, and sox2 during brain regeneration.…”

Section: Global Gene Expression Changes and Enriched Pathways At The Early Stages Of Tectum Regenerationmentioning

confidence: 99%

Transcriptome Analyses Reveal IL6/Stat3 Signaling Involvement in Radial Glia Proliferation After Stab Wound Injury in the Adult Zebrafish Optic Tectum

Shimizu

Kiyooka

Ohshima

2021

Front. Cell Dev. Biol.

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Adult zebrafish have many neurogenic niches and a high capacity for central nervous system regeneration compared to mammals, including humans and rodents. The majority of radial glia (RG) in the zebrafish optic tectum are quiescent under physiological conditions; however, stab wound injury induces their proliferation and differentiation into newborn neurons. Although previous studies have functionally analyzed the molecular mechanisms of RG proliferation and differentiation and have performed single-cell transcriptomic analyses around the peak of RG proliferation, the cellular response and changes in global gene expression during the early stages of tectum regeneration remain poorly understood. In this study, we performed histological analyses which revealed an increase in isolectin B4+ macrophages prior to the induction of RG proliferation. Moreover, transcriptome and pathway analyses based on differentially expressed genes identified various enriched pathways, including apoptosis, the innate immune system, cell proliferation, cytokine signaling, p53 signaling, and IL6/Jak-Stat signaling. In particular, we found that Stat3 inhibition suppressed RG proliferation after stab wound injury and that IL6 administration into cerebroventricular fluid activates RG proliferation without causing injury. Together, the findings of these transcriptomic and functional analyses reveal that IL6/Stat3 signaling is an initial trigger of RG activation during optic tectum regeneration.

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“…NE cells are proliferative cells that produce neurons, RG, and oligodendrocytes, whereas most of RG are quiescent ( Alunni et al, 2010 ; Ito et al, 2010 ; Takeuchi and Okubo, 2013 ; Galant et al, 2016 ; Dambroise et al, 2017 ). Previous studies showed that RG proliferation and differentiation into newborn neurons are induced in response to injury in young adult zebrafish (2–4 months old) ( Shimizu et al, 2018 ; Ueda et al, 2018 ; Yu and He, 2019 ; Kiyooka et al, 2020 ). In contrast, the regenerative responses in the medaka tectum remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Differential Regenerative Capacity of the Optic Tectum of Adult Medaka and Zebrafish

Shimizu

Kawasaki

2021

Front. Cell Dev. Biol.

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Zebrafish have superior regenerative capacity in the central nervous system (CNS) compared to mammals. In contrast, medaka were shown to have low regenerative capacity in the adult heart and larval retina, despite the well-documented high tissue regenerative ability of teleosts. Nevertheless, medaka and zebrafish share similar brain structures and biological features to those of mammals. Hence, this study aimed to compare the neural stem cell (NSC) responses and regenerative capacity in the optic tectum of adult medaka and zebrafish after stab wound injury. Limited neuronal differentiation was observed in the injured medaka, though the proliferation of radial glia (RG) was induced in response to tectum injury. Moreover, the expression of the pro-regenerative transcriptional factors ascl1a and oct4 was not enhanced in the injured medaka, unlike in zebrafish, whereas expression of sox2 and stat3 was upregulated in both fish models. Of note, glial scar-like structures composed of GFAP+ radial fibers were observed in the injured area of medaka at 14 days post injury (dpi). Altogether, these findings suggest that the adult medaka brain has low regenerative capacity with limited neuronal generation and scar formation. Hence, medaka represent an attractive model for investigating and evaluating critical factors for brain regeneration.

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Histone deacetylase inhibition promotes regenerative neurogenesis after stab wound injury in the adult zebrafish optic tectum

Cited by 12 publications

References 29 publications

Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates

Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates

Transcriptome Analyses Reveal IL6/Stat3 Signaling Involvement in Radial Glia Proliferation After Stab Wound Injury in the Adult Zebrafish Optic Tectum

Differential Regenerative Capacity of the Optic Tectum of Adult Medaka and Zebrafish

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