Genome-wide DNA methylation of lesional and peri-lesional skin in vitiligo: a comparative and integrated analysis of multi-omics in Chinese population

Several studies have emphasized the role of DNA methylation in vitiligo. However, its profile in human skin of individuals with vitiligo remains unknown. Here, we aimed to study the DNA methylation profile of vitiligo using pairwise comparisons of lesions, peri-lesions, and healthy skin. We investig...

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Bibliographic Details
Published in:Human genetics Vol. 143; no. 2; pp. 137 - 149
Main Authors: Liu, Lin, Xue, Yuzhou, Li, Yuxin, Chen, Yangmei, Pan, Xingyu, Huang, Yujing, Chen, Tingqiao, Zhong, Judan, Shao, Xinyi, Pu, Yihuan, Chen, Jin
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2024
Springer
Springer Nature B.V
Subjects:
Biomedical and Life Sciences
Biomedicine
Cell division
Cell interactions
circadian rhythm
Circadian rhythms
Comparative analysis
data collection
DNA
DNA methylation
Extracellular matrix
fatty acid metabolism
Fatty acids
Gene Function
Genes
Genomes
Genomics
Human Genetics
Keratinocytes
Melanocytes
Metabolic Diseases
Methylation
Molecular Medicine
multiomics
Original Investigation
pathogenesis
peroxidase
Pigmentation
Population studies
RNA
Skin
skin (animal)
Skin diseases
synapse
Synapses
therapeutics
transcriptome
Transcriptomes
Vitiligo
ISSN:0340-6717, 1432-1203, 1432-1203
Online Access:Get full text
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Summary:Several studies have emphasized the role of DNA methylation in vitiligo. However, its profile in human skin of individuals with vitiligo remains unknown. Here, we aimed to study the DNA methylation profile of vitiligo using pairwise comparisons of lesions, peri-lesions, and healthy skin. We investigated DNA methylation levels in six lesional skin, six peri-lesional skin, and eight healthy skin samples using an Illumina 850 K methylation chip. We then integrated DNA methylation data with transcriptome data to identify differentially methylated and expressed genes (DMEGs) and analyzed their functional enrichment. Subsequently, we compared the methylation and transcriptome characteristics of all skin samples, and the related genes were further studied using scRNA-seq data. Finally, validation was performed using an external dataset. We observed more DNA hypomethylated sites in patients with vitiligo. Further integrated analysis identified 264 DMEGs that were mainly functionally enriched in cell division, pigmentation, circadian rhythm, fatty acid metabolism, peroxidase activity, synapse regulation, and extracellular matrix. In addition, in the peri-lesional skin, we found that methylation levels of 102 DMEGs differed prior to changes in their transcription levels and identified 16 key pre-DMEGs ( ANLN, CDCA3, CENPA, DEPDC1, ECT2, DEPDC1B , HMMR, KIF18A, KIF18B, TTK, KIF23, DCT, EDNRB, MITF, OCA2, and TYRP1) . Single-cell RNA analysis showed that these genes were associated with cycling keratinocytes and melanocytes. Further analysis of cellular communication indicated the involvement of the extracellular matrix. The expression of related genes was verified using an external dataset. To the best of our knowledge, this is the first study to report a comprehensive DNA methylation profile of clinical vitiligo and peri-lesional skin. These findings would contribute to future research on the pathogenesis of vitiligo and potential therapeutic strategies.
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ISSN:0340-6717
1432-1203
1432-1203
DOI:10.1007/s00439-023-02630-5