Forward single‐cell sequencing into clinical application: Understanding of ageing and rejuvenation from clinical observation to single‐cell solution

Yan, Furong; Li, Zhangping; Powell, Charles A.; Wang, Xiangdong

doi:10.1002/ctm2.827

Cited by 6 publications

(6 citation statements)

References 28 publications

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“…149 Our data suggest that local astrocyte-macrophage/monocyte interactions in LRRK2 G2019S mice promote astrocyte-dependent mechanisms of immune cell trafficking within the CNS during ageing and low-grade inflammation. However, further studies carried out in PD-specific brain regions, peripheral tissues and blood are clearly needed to explore in this LRRK2-inflammatory model, "in situ" cell-cell interactions and novel signaling mechanisms that might be useful to develop ageing-specific therapeutic targets 150 .…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this this version posted September 3, 2022. ; https://doi.org/10.1101/2022.09.01.505977 doi: bioRxiv preprint peripheral tissues and blood are clearly needed to explore in this LRRK2-inflammatory model, "in situ" cell-cell interactions and novel signaling mechanisms that might be useful to develop ageing-specific therapeutic targets 150 .…”

Section: Discussionmentioning

confidence: 99%

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LRRK2-G2019S Synergizes with Ageing and Low-Grade Inflammation to Promote Gut and Peripheral Immune Cell Activation that Precede Nigrostriatal Degeneration

Giachino

Tirolo

Caniglia

et al. 2022

Preprint

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Background: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson's disease (PD). The incomplete penetrance of LRRK2 mutations suggest that additional hits are required for disease onset. We hypothesized that chronic low-grade inflammation interacts with LRRK2 G2019S, the most frequent PD-associated mutation, to activate peripheral and central immune reactions and drive age-dependent neurodegeneration. Methods and Results: We exposed wild-type and LRRK2 G2019S mice to a low chronic dose of lipopolysaccharide, and we performed a longitudinal analysis of central and peripheral immune reactions and neurodegeneration. Low-dose inflammation triggered nigrostriatal degeneration, macrophage/monocyte brain infiltration, and astro-/microgliosis. LRRK2 G2019S mice showed an early dysregulation of peripheral cytokines, increased CD4+ T-cell infiltration and α-synuclein aggregation in the colon. Interestingly, peripheral immune activation and colonic α-synuclein aggregation precede astro-/microgliosis and neurodegeneration. Conclusions: Our study suggests an early role of the peripheral immune system and the gut in LRRK2 PD and provides a novel model to study early therapeutic immune targets and biomarkers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LRRK2-G2019S Synergizes with Ageing and Low-Grade Inflammation to Promote Gut and Peripheral Immune Cell Activation that Precede Nigrostriatal Degeneration

Giachino

Tirolo

Caniglia

et al. 2022

Preprint

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“…However, further studies carried out in PD-specific brain regions, peripheral tissues and blood are clearly needed to explore in this LRRK2-inflammatory model, "in situ" cell-cell interactions and novel signaling mechanisms that might be useful to develop ageing-specific therapeutic targets. 150 With regard to microglia, both in vitro and in vivo studies show that LRRK2 modulate microglia inflammatory responses. 53,55,56,[151][152][153] Recent studies suggest that LRRK2 levels in microglia may not have a direct effect on neuroinflammation in PD, as in vivo injection of a high acute dose of LPS failed to increase microglia LRRK2 protein levels in R1441C and G2019S young adult mice 70 .…”

Section: Discussionmentioning

confidence: 99%

LRRK2-G2019S Synergizes With Ageing and Low-Grade Inflammation to Promote Gut and Peripheral Immune Cell Activation That Precede Nigrostriatal Degeneration

Marchetti

Giachino

Tirolo

et al. 2022

Preprint

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Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson's disease (PD). The incomplete penetrance of LRRK2 mutations suggest that additional hits are required for disease onset. We hypothesized that chronic low-grade inflammation interacts with LRRK2 G2019S, the most frequent PD-associated mutation, to activate peripheral and central immune reactions and drive age-dependent neurodegeneration. We exposed wild-type and LRRK2 G2019S mice to a low chronic dose of lipopolysaccharide and performed a longitudinal analysis of central and peripheral immune reactions and neurodegeneration. Low-dose inflammation triggered nigrostriatal degeneration, peripheral monocyte infiltration, and astro-/microgliosis. LRRK2 G2019S mice showed an early dysregulation of peripheral cytokines as well as increased CD4+ T-cell infiltration and α-synuclein aggregation in the colon. Peripheral immune activation and colonic α-synuclein aggregation preceded brain inflammation and degeneration. Our study suggests an early role of the peripheral immune system and the gut in LRRK2 PD and provides a novel model to study early therapeutic immune targets and biomarkers.

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“…In the past few years, the emergence of second‐generation sequencing has made it easier to identify marker genes associated with a range of diseases. Single‐cell sequencing is also used to explore potential cell types and processes in human diseases (Jovic et al, 2022; Yan et al, 2022; Zhou et al, 2021). These have laid a powerful platform for constructing new diagnostic models related to cryptorchidism genes.…”

Section: Introductionmentioning

confidence: 99%

Construction and analysis of a joint diagnostic model of machine learning for cryptorchidism based on single‐cell sequencing

Chen,

Zhou,

et al. 2024

Birth Defects Research

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BackgroundCryptorchidism is a condition in which one or both of a baby's testicles do not fully descend into the bottom of the scrotum. Newborns with cryptorchidism are at increased risk of developing infertility later in life. The aim of this study was to develop a novel diagnostic model for cryptorchidism and to identify new biomarkers associated with cryptorchidism.MethodsThe study data were obtained from RNA sequencing data of cryptorchid patients from Nantong University Hospital and the Gene Expression Omnibus (GEO) database. Differential expression analysis was used to obtain differentially expressed genes (DEGs) between the control and cryptorchid groups. These DEGs were analyzed for their functions by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment using GSEA software. Random Forest algorithm was used to screen central genes based on these DEGs. Neuralnet software package was used to develop artificial neural network models. Based on clinical data, receiver operating characteristic (ROC) was used to validate the models. Single‐cell sequencing analysis was used for the pathogenesis of cryptorchidism.ResultsWe obtained a total of 525 important DEGs related to cryptorchidism, which are mainly associated with biological functions such as supramolecular complexes and microtubule cytoskeleton. Random forest approach screening obtained eight hub genes. A neural network based on the hub genes showed a 100% success rate of the model. Finally, single‐cell sequencing analysis validated the hub genes.ConclusionWe developed a novel diagnostic model for cryptorchidism using artificial neural networks and validated its utility as an effective diagnostic tool.

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Forward single‐cell sequencing into clinical application: Understanding of ageing and rejuvenation from clinical observation to single‐cell solution

Cited by 6 publications

References 28 publications

LRRK2-G2019S Synergizes with Ageing and Low-Grade Inflammation to Promote Gut and Peripheral Immune Cell Activation that Precede Nigrostriatal Degeneration

LRRK2-G2019S Synergizes with Ageing and Low-Grade Inflammation to Promote Gut and Peripheral Immune Cell Activation that Precede Nigrostriatal Degeneration

LRRK2-G2019S Synergizes With Ageing and Low-Grade Inflammation to Promote Gut and Peripheral Immune Cell Activation That Precede Nigrostriatal Degeneration

Construction and analysis of a joint diagnostic model of machine learning for cryptorchidism based on single‐cell sequencing

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