Exploring the role of RALYL in Alzheimer’s disease reserve by network-based approaches

Zhang, Yixuan; Wang, Jiali; Liu, Xiaoquan; Liu, Haochen

doi:10.1186/s13195-020-00733-z

Cited by 10 publications

(13 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the top ten upregulated genes were genes known for their roles in neurodevelopment including Heparan Sulfate 6-O-Sulfotransferase 3 ( Hs6st3 ), Adhesion G Protein-Coupled Receptor L3 ( Adgrl3 ), Contactin 5 ( Cntn5 ), and Neuregulin 1 ( Nrg1 ) ( Mei and Xiong, 2008 ; Cocchi et al, 2016 ; El Hajj et al, 2017 ; Moon and Zhao, 2021 ). In addition, SCA1 PCs had increased expression of RALY RNA Binding Protein-like (Ralyl) ,which is known as an Alzheimer’s disease cognitive reserve gene ( Zhang et al, 2020 ) ( Figures 2A–C ).…”

Section: Resultsmentioning

confidence: 99%

Single nuclei RNA sequencing investigation of the Purkinje cell and glial changes in the cerebellum of transgenic Spinocerebellar ataxia type 1 mice

Borgenheimer

Hamel

Sheeler

et al. 2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Glial cells constitute half the population of the human brain and are essential for normal brain function. Most, if not all, brain diseases are characterized by reactive gliosis, a process by which glial cells respond and contribute to neuronal pathology. Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease characterized by a severe degeneration of cerebellar Purkinje cells (PCs) and cerebellar gliosis. SCA1 is caused by an abnormal expansion of CAG repeats in the gene Ataxin1 (ATXN1). While several studies reported the effects of mutant ATXN1 in Purkinje cells, it remains unclear how cerebellar glia respond to dysfunctional Purkinje cells in SCA1. To address this question, we performed single nuclei RNA sequencing (snRNA seq) on cerebella of early stage Pcp2-ATXN1[82Q] mice, a transgenic SCA1 mouse model expressing mutant ATXN1 only in Purkinje cells. We found no changes in neuronal and glial proportions in the SCA1 cerebellum at this early disease stage compared to wild-type controls. Importantly, we observed profound non-cell autonomous and potentially neuroprotective reactive gene and pathway alterations in Bergmann glia, velate astrocytes, and oligodendrocytes in response to Purkinje cell dysfunction.

show abstract

Section: Resultsmentioning

confidence: 99%

Single nuclei RNA sequencing investigation of the Purkinje cell and glial changes in the cerebellum of transgenic Spinocerebellar ataxia type 1 mice

Borgenheimer

Hamel

Sheeler

et al. 2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Among top ten upregulated genes were Heparan Sulfate 6-O-Sulfotransferase 3 ( Hs6st3 ), Adhesion G Protein-Coupled Receptor L3 ( Adgrl3 ), Contactin 5 ( Cntn5 ), and Neuregulin 1 ( Nrg1 ) known for their roles in neurodevelopment [47][48][49][50]. In addition, SCA1 PCs had increased expression of RALY RNA Binding Protein-like (Ralyl) known as Alzheimer’s disease cognitive reserve gene [51] ( Figures 2A-C ). Among upregulated genes were also three vacuolar V-type ATP-ase subunits ( Atp6v0c , Atpgv0a1 , and Atp6v1h ) and Slc32a1 , encoding vesicular GABA and Glycine Transporter (VGAT) indicating that synaptic vesicles SCA1 PCs may have increased GABA content.…”

Section: Resultsmentioning

confidence: 99%

“…For PCs we validated the findings from previous studies but also identified novel, potentially compensatory gene expression changes such as increased expression of Ralyl , Atp6v0c , Atpgv0a1 , Atp6v1h , Atp6v and Slc32a1. Ralyl is an RNA binding protein known for its neuroprotective role in Alzheimer’s [51]. Increased expression of three vacuolar V-type ATP-ase subunits ( Atp6v0c , Atpgv0a1 , and Atp6v1h ) that provide electrochemical gradient to fill synaptic vesicles with GABA and Slc32a1 , encoding vesicular GABA and Glycine Transporter (VGAT) that transports GABA in the vesicles may suggest increased GABA content in PCs synaptic vesicle.…”

Section: Discussionmentioning

confidence: 99%

Single-nuclei RNA sequencing uncovers non-cell autonomous changes in cerebellar astrocytes and oligodendrocytes that may contribute to Spinocerebellar Ataxia Type 1 (SCA1) pathogenesis

Borgenheimer

Zhang

Cvetanović

2021

Preprint

View full text Add to dashboard Cite

Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by an abnormal expansion of CAG repeats in the gene Ataxin1 (ATXN1). While mutant ATXN1 is expressed throughout the brain, SCA1 is characterized by severe degeneration of cerebellar Purkinje cells (PCs) and cerebellar gliosis. It is likely that cerebellar microenvironment and in particular glial cells contribute to the Purkinje cell specific vulnerability in SCA1. We have used single nuclei RNA sequencing (snRNA seq) to uncover effects of mutant ATXN1 on PCs gene expression changes as well as non-cell autonomous changes in glial cells transcriptomes in cerebella of Pcp2-ATXN1[82Q] mice, a transgenic SCA1 mouse model expressing mutant ATXN1 only in PCs cells

show abstract

“…Notably, the Ralyl expression decreases with Alzheimer's progression. Subjects with Alzheimer's disease reserves show significantly higher Ralyl expression compared with those without Alzheimer's disease reserves (Zhang et al, 2020). Ralyl is related to cancer cell metastasis and poor prognosis in patients with liver cancer.…”

Section: Granule Cell Genementioning

confidence: 93%

“…The Raly-like recognition motif (Ralyl) is identified as an important characteristic gene by the mRMR, and its encoded RNA binding protein affects embryonic development (Ji et al, 2003a). A previous study pointed out that Ralyl may be related to Alzheimer's disease (Zhang et al, 2020). Researchers revealed that Ralyl is a hub gene in the brain transcriptome module of patients with Alzheimer's disease and is highly associated with Alzheimer's reserve-related phenotypes.…”

Section: Granule Cell Genementioning

confidence: 99%

Exploring the Genomic Patterns in Human and Mouse Cerebellums Via Single-Cell Sequencing and Machine Learning Method

Wang

Liao

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

In mammals, the cerebellum plays an important role in movement control. Cellular research reveals that the cerebellum involves a variety of sub-cell types, including Golgi, granule, interneuron, and unipolar brush cells. The functional characteristics of cerebellar cells exhibit considerable differences among diverse mammalian species, reflecting a potential development and evolution of nervous system. In this study, we aimed to recognize the transcriptional differences between human and mouse cerebellum in four cerebellar sub-cell types by using single-cell sequencing data and machine learning methods. A total of 321,387 single-cell sequencing data were used. The 321,387 cells included 4 cell types, i.e., Golgi (5,048, 1.57%), granule (250,307, 77.88%), interneuron (60,526, 18.83%), and unipolar brush (5,506, 1.72%) cells. Our results showed that by using gene expression profiles as features, the optimal classification model could achieve very high even perfect performance for Golgi, granule, interneuron, and unipolar brush cells, respectively, suggesting a remarkable difference between the genomic profiles of human and mouse. Furthermore, a group of related genes and rules contributing to the classification was identified, which might provide helpful information for deepening the understanding of cerebellar cell heterogeneity and evolution.

show abstract

Exploring the role of RALYL in Alzheimer’s disease reserve by network-based approaches

Cited by 10 publications

References 45 publications

Single nuclei RNA sequencing investigation of the Purkinje cell and glial changes in the cerebellum of transgenic Spinocerebellar ataxia type 1 mice

Single nuclei RNA sequencing investigation of the Purkinje cell and glial changes in the cerebellum of transgenic Spinocerebellar ataxia type 1 mice

Single-nuclei RNA sequencing uncovers non-cell autonomous changes in cerebellar astrocytes and oligodendrocytes that may contribute to Spinocerebellar Ataxia Type 1 (SCA1) pathogenesis

Exploring the Genomic Patterns in Human and Mouse Cerebellums Via Single-Cell Sequencing and Machine Learning Method

Contact Info

Product

Resources

About