Epigenetic mechanisms in neurogenesis

Yao, Bing; Christian, Kimberly M.; He, Chuan; Jin, Peng; Ming, Guo Li; Song, Hongjun

doi:10.1038/nrn.2016.70

Cited by 311 publications

(261 citation statements)

References 185 publications

(226 reference statements)

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“…Because epigenetic regulators can affect transcription on a genome-wide scale, yet do so in a cell-type-specific and context-specific manner, they represent interesting targets to promote neural repair. Whereas the role of epigenetics in regulating CNS gene expression during development 163 or neural activity is being actively investigated 164 , its role in axon regeneration is only emerging.…”

Section: Epigenetic Integration In the Nucleusmentioning

confidence: 99%

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Intrinsic mechanisms of neuronal axon regeneration

2018

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Permanent disabilities following CNS injuries result from the failure of injured axons to regenerate and rebuild functional connections with their original targets. By contrast, injury to peripheral nerves is followed by robust regeneration, which can lead to recovery of sensory and motor functions. This regenerative response requires the induction of widespread transcriptional and epigenetic changes in injured neurons. Considerable progress has been made in recent years in understanding how peripheral axon injury elicits these widespread changes through the coordinated actions of transcription factors, epigenetic modifiers and, to a lesser extent, microRNAs. Although many questions remain about the interplay between these mechanisms, these new findings provide important insights into the pivotal role of coordinated gene expression and chromatin remodelling in the neuronal response to injury.

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Section: Epigenetic Integration In the Nucleusmentioning

confidence: 99%

“…This modification, which is primarily deposited at CpG dinucleotides, is dynamically regulated during neuronal development and in response to various stimuli 163,164 . Three DNA (cytosine-5)-methyltransferase (DNMT) enzymes — DNMT1, DNMT3A and DNMT3B — are responsible for catalysing this reaction.…”

Section: Epigenetic Integration In the Nucleusmentioning

confidence: 99%

Intrinsic mechanisms of neuronal axon regeneration

2018

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“…Furthermore, recent research has uncovered the true complexity of the range of modifications occurring at these 'methylation' sites on DNA [52] (Figure 2 marks, 5-formylcytosine (5fC), derived from ten-eleven translocation gene protein 1 (TET1)-mediated oxidation of 5-hydroxymethylation (5-hmC), has been shown to be associated with the recruitment of the transcription factor ING1 (inhibitor of growth family member 1). This association has been linked to the transcription of essential genes within the mPFC that are required for successful fear extinction training in mice [53].…”

Section: Histone and Dna Methylationmentioning

confidence: 99%

Molecular and Epigenetic Mechanisms Underlying Cognitive and Adaptive Responses to Stress

et al. 2017

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Consolidation of contextual memories after a stressful encounter is essential for the survival of an organism and in allowing a more appropriate response to be elicited should the perceived threat reoccur. Recent evidence has explored the complex role that epigenetic mechanisms play in the formation of such memories, and the underlying signaling pathways are becoming more apparent. The glucocorticoid receptor (GR) has been shown to play a key role in these events having both genomic and non-genomic actions in the brain. GR has been shown to interact with the extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) signaling pathway which, in concert, drives epigenetic modifications and chromatin remodeling, resulting in gene induction and memory consolidation. Evidence indicates that stressful events can have an effect on the offspring in utero, and that epigenetic marks altered early in life may persist into adulthood. A new and controversial area of research, however, suggests that epigenetic modifications could be inherited through the germline, a concept known as transgenerational epigenetics. This review explores the role that epigenetic processes play in the central nervous system, specifically in the consolidation of stress-induced memories, the concept of transgenerational epigenetic inheritance, and the potential role of epigenetics in revolutionizing the treatment of stress-related disorders through the emerging field of pharmacoepigenetics and personalized medical treatment.

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“…Defined substages therefore depend on a delicate balance of extrinsic and intrinsic signaling. In this issue, Jing and colleagues (2) explore this balance using RNA sequencing (RNA-seq) 3 to create a detailed blueprint of transcriptome dynamics during differentiation of human embryonic stem cells (hESCs) into the neural fate, and they identified five distinct stages throughout the process (2). These data provide compelling evidence that differentiation consists of multiple unique steps defined by both extrinsic and intrinsic signals.…”

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confidence: 99%

“…E-mail: shongjun@ pennmedicine.upenn.edu. 3 The abbreviations used are: RNA-seq, RNA sequencing; hESC, human embryonic stem cell; TF, transcription factor.…”

mentioning

confidence: 99%

Stem cells take the stairs

Vissers

Ming

Song

2017

Journal of Biological Chemistry

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Edited by Xiao-Fan WangHuman embryonic stem cells progress through multiple stages in their path to neural differentiation, but the steps taken along the way are difficult to distinguish, limiting our understanding of this important process. Jing and colleagues (2) now report comprehensive analyses of transcriptome dynamics during this process that reveal five discrete stages, defined in part by highly connected transcription factor networks that link progressive stages. Surprisingly, the third stage, which appears to be critical for neural fate commitment, depends almost entirely on intracellular signaling.One of the major challenges in developmental biology is to explicitly define unique stages and dynamic transitions within the stem cell differentiation process. This is largely because, as Conrad Waddington famously depicted in his epigenetic landscape, gene expression changes and cellular identity appear to roll down a hill of differentiation instead of taking easily defined steps (1). However, just as a ramp may become a pixelated staircase when more details are defined, the field has begun to identify small, definable substages of differentiation by in-depth analysis of molecular landscapes (1). These landscapes are regulated by both intrinsic signals (i.e. molecular events originating within cells) and extrinsic signals (cues from the external niche that feed information to the cell). Defined substages therefore depend on a delicate balance of extrinsic and intrinsic signaling. In this issue, Jing and colleagues (2) explore this balance using RNA sequencing (RNA-seq) 3 to create a detailed blueprint of transcriptome dynamics during differentiation of human embryonic stem cells (hESCs) into the neural fate, and they identified five distinct stages throughout the process (2). These data provide compelling evidence that differentiation consists of multiple unique steps defined by both extrinsic and intrinsic signals.Among developmental processes, neurogenesis is particularly complicated due to its dynamic spatiotemporal progression, and errors in this intricate process could lead to developmental disorders such as autism or schizophrenia (3). Historically, rodents and amphibians were used to study brain development, but gaining a full picture of unique features of human brain development requires a more accurate human model. In particular, hESCs and induced pluripotent stem cells have provided a very useful platform to understand basic processes of human brain development and to manipulate specific genes to examine their functional roles. Previous work, including data from transcriptome analysis by RNA-seq, has created snapshots of the molecular state of the cell during hESC neural differentiation but only at a low resolution (4, 5).To obtain a systematic view of neural development with a high temporal resolution, Jing and colleagues (2) modified a published protocol for hESC neural differentiation (6), so they could analyze cells across several developmental stages en route to cortical projection neurons (F...

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Epigenetic mechanisms in neurogenesis

Cited by 311 publications

References 185 publications

Intrinsic mechanisms of neuronal axon regeneration

Intrinsic mechanisms of neuronal axon regeneration

Molecular and Epigenetic Mechanisms Underlying Cognitive and Adaptive Responses to Stress

Stem cells take the stairs

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