KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure

Bi, Jinfang; Wang, Wenbin; Zhang, Meng; Zhang, Baoying; Liu, Man; Su, Guanghao; Chen, Fuquan; Chen, Bohan; Shi, Tao; Zheng, Yusheng; Zhao, Xin; Zhao, Zhongfang; Shi, Jiandang; Zhang, Lei; Lu, Wange

doi:10.1093/nar/gkac1118

Cited by 6 publications

(4 citation statements)

References 77 publications

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“…It plays a critical role in maintaining the structural integrity of the blood–brain barrier and the proper functioning of brain vasculature [ 101 ]. KLF4 is a transcription factor that regulates the expression of various genes involved in cell proliferation, differentiation, and development [ 102 , 103 ]. In the brain, KLF4 is important for neuronal survival, synaptic plasticity, and neuroinflammatory responses.…”

Section: Resultsmentioning

confidence: 99%

Investigating Neuron Degeneration in Huntington’s Disease Using RNA-Seq Based Transcriptome Study

Sneha,

Dharshini,

Taguchi

et al. 2023

Genes

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Huntington’s disease (HD) is a progressive neurodegenerative disorder caused due to a CAG repeat expansion in the huntingtin (HTT) gene. The primary symptoms of HD include motor dysfunction such as chorea, dystonia, and involuntary movements. The primary motor cortex (BA4) is the key brain region responsible for executing motor/movement activities. Investigating patient and control samples from the BA4 region will provide a deeper understanding of the genes responsible for neuron degeneration and help to identify potential markers. Previous studies have focused on overall differential gene expression and associated biological functions. In this study, we illustrate the relationship between variants and differentially expressed genes/transcripts. We identified variants and their associated genes along with the quantification of genes and transcripts. We also predicted the effect of variants on various regulatory activities and found that many variants are regulating gene expression. Variants affecting miRNA and its targets are also highlighted in our study. Co-expression network studies revealed the role of novel genes. Function interaction network analysis unveiled the importance of genes involved in vesicle-mediated transport. From this unified approach, we propose that genes expressed in immune cells are crucial for reducing neuron death in HD.

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Section: Resultsmentioning

confidence: 99%

Investigating Neuron Degeneration in Huntington’s Disease Using RNA-Seq Based Transcriptome Study

Sneha,

Dharshini,

Taguchi

et al. 2023

Genes

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“…This dysregulation can result in aberrant neural progenitor dynamics, potentially leading to the generation of non-functional or improperly differentiated neurons. Impaired klf4 function may lead to disrupted synaptic formation and connectivity [246,247]. This disruption could contribute to cognitive and functional de cits observed in neurodegenerative conditions.…”

Section: Klf4mentioning

confidence: 99%

Investigating How Inflammation Involving NF-κB Signaling Disrupts the Genetic Architecture of Neurons/Neural Stem Cells and Fuels Neurodegeneration

Shafi,

Rajpar,

Yaqoob

et al. 2024

Preprint

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Background: Understanding how inflammation disrupts neural stem cells and neuronal genetic architecture is crucial. This investigation explores these mechanisms, aiming to decipher the role of inflammation in disrupting neuronal genetic architecture. Unraveling these complexities may reveal therapeutic targets, offering hope for precision interventions to impede or slow the progression of debilitating neurodegenerative conditions.Methods: Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving NF-κB and neurogenic genes/signaling pathways/transcription factors. They were investigated in the study to unravel how inflammation disrupts the neural stem cells (NSCs) and neuronal genetic architecture, and how this process fuels the development of neurodegeneration. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).Results: This study reveals how NF-κB activation plays a central role in inflammation-induced disruption, mediating transcriptional dysregulation of key neurogenic factors like Ngn1, NeuroD, and PDGF, compromising the neurogenic code. Downregulation of neurotrophic factors, notably BDNF, increases neuronal vulnerability to apoptotic pathways, accelerating neurodegeneration. Inflammatory processes extend to the genomic landscape, affecting genes crucial for neurogenesis and synaptic function, contributing to observed synaptic dysfunction in neurodegenerative diseases. Furthermore, inflammation disrupts NSCs, impairing neurogenesis and compromising neural progenitor dynamics, diminishing the regenerative potential of the nervous system. Identified therapeutic strategies include precision targeting of NF-κB, restoration of neurotrophic support, and interventions promoting proper gene expression and neurogenesis, offering promising avenues for mitigating inflammation-induced damage and halting neurodegenerative progression.Conclusion: This study investigates the intricate impact of inflammation on neural stem cells (NSCs) and neuronal genetic architecture, providing insights into the pathogenesis disrupting neuronal architecture. NF-κB-mediated disruptions compromise neurotrophic support, impair neurogenesis, induce synaptic dysfunction, and enhance vulnerability to apoptosis. This orchestrated genomic dysregulation contributes to the progression of neurodegenerative diseases. Therapeutically, precision targeting of NF-κB, restoration of neurotrophic support, and promotion of neurogenesis emerge as promising strategies to mitigate inflammation-induced damage, offering potential avenues for interventions to impede the neurodegenerative cascade.

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“…ChIP-seq assay was performed as previously described [100]. Cells were cross-linked with 1% formaldehyde at RT for 10 min and quenched in 125 mM glycine for 5 min.…”

Section: Chip-seqmentioning

confidence: 99%

Three-Dimensional Gene Regulation Network in Glioblastoma Ferroptosis

Liu,

Wang,

Zhang

et al. 2023

IJMS

Self Cite

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Ferroptosis is an iron-dependent form of cell death, which is reported to be associated with glioma progression and drug sensitivity. Targeting ferroptosis is a potential therapeutic approach for glioma. However, the molecular mechanism of glioma cell ferroptosis is not clear. In this study, we profile the change of 3D chromatin structure in glioblastoma ferroptosis by using HiChIP and study the 3D gene regulation network in glioblastoma ferroptosis. A combination of an analysis of HiChIP and RNA-seq data suggests that change of chromatin loops mediated by 3D chromatin structure regulates gene expressions in glioblastoma ferroptosis. Genes that are regulated by 3D chromatin structures include genes that were reported to function in ferroptosis, like HDM2 and TXNRD1. We propose a new regulatory mechanism governing glioblastoma cell ferroptosis by 3D chromatin structure.

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KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure

Cited by 6 publications

References 77 publications

Investigating Neuron Degeneration in Huntington’s Disease Using RNA-Seq Based Transcriptome Study

Investigating Neuron Degeneration in Huntington’s Disease Using RNA-Seq Based Transcriptome Study

Investigating How Inflammation Involving NF-κB Signaling Disrupts the Genetic Architecture of Neurons/Neural Stem Cells and Fuels Neurodegeneration

Three-Dimensional Gene Regulation Network in Glioblastoma Ferroptosis

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