首页|Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

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Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain origins.Emerging evidence implicates N6-methyladenosine(m6A)modification in ALS pathogenesis.Methylated RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography-mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication changes.Analysis of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in ALS.Serum proteome analysis demonstrated the role of dysregulated immune cell migration in ALS.Cell type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were observed.Intercellular communication between neurons and glial cells was selectively altered in ALS CNS.This integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

amyotrophic lateral sclerosisN6-methyladenosineepi-transcriptomeproteomesingle cell RNA sequencing analysisCX3CR1

Di He、Xunzhe Yang、Liyang Liu、Dongchao Shen、Qing Liu、Mingsheng Liu、Xue Zhang、Liying Cui

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Department of Neurology,Peking Union Medical College Hospital(PUMCH),Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China

Medical Doctor Program,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730,China

McKusick-Zhang Center for Genetic Medicine,State Key Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine,Peking Union Medical College,Beijing 100730,China

Neuroscience Center,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China

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Strategic Priority Research Program(Pilot study)of the Chinese Academy of SciencesChinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical SciencesChinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical SciencesNational High Level Hospital Clinical Research Funding北京市自然科学基金国家自然科学基金

XDB390400002021-I2M-1-0032021-I2M-1-0342022-PUMCH-B-017720215881971293

2024

10.1007/s11684-023-1035-5

医学前沿
高等教育出版社

医学前沿

CSTPCD
影响因子：1.362
ISSN：2095-0217
年,卷(期)：2024.18(2)
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