Potential roles of stem cell marker genes in axon regeneration

Lee, Jin Young; Cho, Yongcheol

doi:10.1038/s12276-020-00553-z

Cited by 8 publications

(7 citation statements)

References 104 publications

(47 reference statements)

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“…PAPPA encodes for the pregnancy-associated plasma protein A, which can cleave insulin-like growth factor binding proteins (IGFBP) to regulate IGF1 availability. rs111891989 is located in an intron of MSI1 , that encodes for an RNA-binding protein which binds to ROBO3 to regulate the midline crossing of pre-cerebellar neurons 27 . rs118017926 is an intronic variant, located in the ZNF462 gene that encodes for zinc-finger transcription factor important for embryonic neurodevelopment 28 .…”

Section: Resultsmentioning

confidence: 99%

Genome-wide association study of cerebellar volume provides insights into heritable mechanisms underlying brain development and mental health

et al. 2022

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Cerebellar volume is highly heritable and associated with neurodevelopmental and neurodegenerative disorders. Understanding the genetic architecture of cerebellar volume may improve our insight into these disorders. This study aims to investigate the convergence of cerebellar volume genetic associations in close detail. A genome-wide associations study for cerebellar volume was performed in a discovery sample of 27,486 individuals from UK Biobank, resulting in 30 genome-wide significant loci and a SNP heritability of 39.82%. We pinpoint the likely causal variants and those that have effects on amino acid sequence or cerebellar gene-expression. Additionally, 85 genome-wide significant genes were detected and tested for convergence onto biological pathways, cerebellar cell types, human evolutionary genes or developmental stages. Local genetic correlations between cerebellar volume and neurodevelopmental and neurodegenerative disorders reveal shared loci with Parkinson’s disease, Alzheimer’s disease and schizophrenia. These results provide insights into the heritable mechanisms that contribute to developing a brain structure important for cognitive functioning and mental health.

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Section: Resultsmentioning

confidence: 99%

Genome-wide association study of cerebellar volume provides insights into heritable mechanisms underlying brain development and mental health

et al. 2022

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“…Regeneration associated genes are neuron-intrinsic factors that stimulate axonal outgrowth after PNI ( Bolin et al, 1995 ; Tsujino et al, 2000 ; Bosse et al, 2001 ; Snider et al, 2002 ; Abe and Cavalli, 2008 ; Sun and He, 2010 ; Van Kesteren et al, 2011 ; Ma and Willis, 2015 ; Chandran et al, 2016 ; Rao and Pearse, 2016 ; Renthal et al, 2020 ; Shiers et al, 2020 ; Suzuki and Ochi, 2020 ; Lee and Cho, 2021 ). RAG genes encoding the activating protein 1 (AP-1) complex and the Sox (sex-determining region Y box) family were upregulated in both sexes.…”

Section: Resultsmentioning

confidence: 99%

“…Nerve regenerative program in damaged PNS afferent axons is orchestrated by neuron-specific RAG genes expressed in DRG ( Bolin et al, 1995 ; Tsujino et al, 2000 ; Bosse et al, 2001 ; Snider et al, 2002 ; Abe and Cavalli, 2008 ; Sun and He, 2010 ; Van Kesteren et al, 2011 ; Ma and Willis, 2015 ; Chandran et al, 2016 ; Rao and Pearse, 2016 ; Renthal et al, 2020 ; Shiers et al, 2020 ; Suzuki and Ochi, 2020 ; Lee and Cho, 2021 ). In agreement, we observed upregulation of critical RAGs, including Atf3, Sox11, Klf6, Sprr1a , and Gal.…”

Section: Discussionmentioning

confidence: 99%

“…Rapid initiation of regeneration is essential to the successful functional repair of sensory neurons in PNI ( Gordon et al, 2003 ; McDonald et al, 2006 ; Zochodne, 2012 ). Within 24 h after sciatic nerve transection in rodents, DRG transcriptome induces neuron-specific regeneration associated genes (RAGs), including activating transcription factor 3 ( Atf3 ), and growth-associated protein ( Gap)43 ( Bolin et al, 1995 ; Tsujino et al, 2000 ; Bosse et al, 2001 ; Snider et al, 2002 ; Sun and He, 2010 ; Van Kesteren et al, 2011 ; Ma and Willis, 2015 ; Chandran et al, 2016 ; Rao and Pearse, 2016 ; Renthal et al, 2020 ; Shiers et al, 2020 ; Suzuki and Ochi, 2020 ; Lee and Cho, 2021 ). Shortly after peripheral nerve injury, the expression of genes encoding cytokines, chemokines, Toll-like receptors (TLRs), matrix metalloproteinases (MMPs), and other mechanistically related proteins increased ( Kim et al, 2012 ; Chernov et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Sexual Dimorphism of Early Transcriptional Reprogramming in Dorsal Root Ganglia After Peripheral Nerve Injury

Chernov

Shubayev

2021

Front. Mol. Neurosci.

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Peripheral nerve injury induces genome-wide transcriptional reprogramming of first-order neurons and auxiliary cells of dorsal root ganglia (DRG). Accumulating experimental evidence suggests that onset and mechanistic principles of post-nerve injury processes are sexually dimorphic. We examined largely understudied aspects of early transcriptional events in DRG within 24 h after sciatic nerve axotomy in mice of both sexes. Using high-depth RNA sequencing (>50 million reads/sample) to pinpoint sexually dimorphic changes related to regeneration, immune response, bioenergy, and sensory functions, we identified a higher number of transcriptional changes in male relative to female DRG. In males, the decline in ion channel transcripts was accompanied by the induction of innate immune cascades via TLR, chemokine, and Csf1-receptor axis and robust regenerative programs driven by Sox, Twist1/2, and Pax5/9 transcription factors. Females demonstrated nerve injury-specific transcriptional co-activation of the actinin 2 network. The predicted upstream regulators and interactive networks highlighted the role of novel epigenetic factors and genetic linkage to sex chromosomes as hallmarks of gene regulation post-axotomy. We implicated epigenetic X chromosome inactivation in the regulation of immune response activity uniquely in females. Sexually dimorphic regulation of MMP/ADAMTS metalloproteinases and their intrinsic X-linked regulator Timp1 contributes to extracellular matrix remodeling integrated with pro-regenerative and immune functions. Lexis1 non-coding RNA involved in LXR-mediated lipid metabolism was identified as a novel nerve injury marker. Together, our data identified unique early response triggers of sex-specific peripheral nerve injury regulation to gain mechanistic insights into the origin of female- and male-prevalent sensory neuropathies.

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“…PAPPA encodes for the pregnancy-associated plasma protein A, which can cleave insulin-like growth factor binding proteins (IGFBP) to regulate IGF1 availability. rs111891989 is located in an intron of MSI1, that encodes for an RNA-binding protein which binds to ROBO3 to regulate midline crossing of pre-cerebellar neurons 31 . rs118017926 is an intronic variant, located in the ZNF462 gene that encodes for zinc-finger transcription factor important for embryonic neurodevelopment 32 .…”

Section: Genomic Location and Functions Of Candidate Cerebellar Volume Snpsmentioning

confidence: 99%

Genome-wide association study of cerebellar volume

Tissink

Lange

Savage

et al. 2021

Preprint

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Cerebellar volume is highly heritable and associated with neurodevelopmental and neurodegenerative disorders. Understanding the genetic architecture of cerebellar volume may improve our insight into these disorders. This study aims to investigate the convergence of cerebellar volume genetic associations in close detail. A genome-wide associations study for cerebellar volume was performed in a sample of 27,486 individuals from UK Biobank, resulting in 29 genome-wide significant loci and a SNP heritability of 39.82%. We pinpoint variants that have effects on amino acid sequence or cerebellar gene-expression. Additionally, 85 genome-wide significant genes were detected and tested for convergence onto biological pathways, cerebellar cell types or developmental stages. Local genetic correlations between cerebellar volume and neurodevelopmental and neurodegenerative disorders reveal shared loci with Parkinson’s disease, Alzheimer’s disease and schizophrenia. These results provide insights into the heritable mechanisms that contribute to developing a brain structure important for cognitive functioning and mental health.

show abstract

Potential roles of stem cell marker genes in axon regeneration

Cited by 8 publications

References 104 publications

Genome-wide association study of cerebellar volume provides insights into heritable mechanisms underlying brain development and mental health

Genome-wide association study of cerebellar volume provides insights into heritable mechanisms underlying brain development and mental health

Sexual Dimorphism of Early Transcriptional Reprogramming in Dorsal Root Ganglia After Peripheral Nerve Injury

Genome-wide association study of cerebellar volume

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