Evaluation of serum and tissue levels of cold-inducible RNA-binding protein in non-segmental Vitiligo

Moftah, Nayera Hassan; Alnos, Huda; Rashed, Laila Ahmed; Hamdino, Mervat

doi:10.1007/s00403-023-02586-6

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…RBPs regulate nearly every aspect of mRNA processing and are important regulators of cellular gene expression. RBPs are also involved in vitiligo pathogenesis [34]. This study is the rst to analyze the expression and regulatory patterns of RBPs in different cell types at the single-cell level in patients with vitiligo and healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

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Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing

Zhang,

Xiang,

Ding

et al. 2023

Preprint

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Background The pathogenesis of vitiligo remains unclear. The genes encoding vitiligo-related RNA-binding proteins (RBPs) and their underlying pathogenic mechanism have not been determined. Methods Single-cell transcriptome sequencing (scRNA-seq) data from the CNCB database was obtained to identify distinct cell types and subpopulations and the relative proportion changes in vitiligo and healthy samples. Using RBP genes for unsupervised clustering, we obtained the specific RBP genes of different cell types in vitiligo and healthy groups. We analyzed the RBP genes in different cell subpopulations, especially melanocytes. Combined with the bulk RNA-seq data of melanocytes, we obtained the different RBP genes from melanocytes and predicted their function. Cell experiments, including gene knockdown, qRT–PCR, western blotting, flow cytometry, oxidative stress, and ferroptosis-related tests, were conducted to explore the role of the key RBP gene SLC3A2 in vitiligo. Results We identified 14 different cell types and 28 cell subpopulations using scRNA-seq data. There is a significant difference in the proportion of each cell subpopulation between the patients with vitiligo and healthy groups. The RBP gene expression is highly heterogeneous; there are significant differences in some cell types, such as keratinocytes, Langerhans, and melanocytes, while there are no significant differences in other cells, such as T cells and fibroblasts in the two groups. The melanocyte-specific RBP genes were enriched in the apoptosis and immune-related pathways in the patients with vitiligo group. Combined with the bulk RNA-seq data of melanocytes, key RBP genes related to melanocytes were identified, including 11 upregulated RBP genes (BST2, CDKN2A, HLA-A, IFIT1, LMF2, RPL12, RPL29, RPL31, RPS19, RPS21, and RPS28) and one downregulated RBP gene (SLC3A2). Cell experiments confirmed melanocyte proliferation decreased, whereas apoptosis increased after SLC3A2 knockdown. SLC3A2 knockdown in melanocytes also decreased the SOD activity and melanin content; increased the Fe2+, ROS, and MDA content; significantly increased the expression levels of TYR and COX2; and decreased the expression levels of GSH and GPX4. Conclusions We identified the RBP genes of different cell subsets in patients with vitiligo and confirmed that downregulating SLC3A2 can promote ferroptosis in melanocytes. These findings provide new insights into the pathogenesis of vitiligo.

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Section: Discussionmentioning

confidence: 99%

“…SLC3A2 is a putative spermidine transporter in melanocytes. SLC3A2 downregulation promotes chondrocyte ferroptosis in osteoarthritis [34]. Whether this gene is involved in melanocyte ferroptosis has not yet been reported; therefore, we chose this gene for further studies.…”

Section: Functional Rbps Are Largely Regulated In Melanocytes Between...mentioning

confidence: 99%

Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing

Zhang,

Xiang,

Ding

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing

Zhang,

Xiang,

Ding

et al. 2024

BMC Genomics

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Background The pathogenesis of vitiligo remains unclear. The genes encoding vitiligo-related RNA-binding proteins (RBPs) and their underlying pathogenic mechanism have not been determined. Results Single-cell transcriptome sequencing (scRNA-seq) data from the CNCB database was obtained to identify distinct cell types and subpopulations and the relative proportion changes in vitiligo and healthy samples. We identified 14 different cell types and 28 cell subpopulations. The proportion of each cell subpopulation significantly differed between the patients with vitiligo and healthy groups. Using RBP genes for unsupervised clustering, we obtained the specific RBP genes of different cell types in vitiligo and healthy groups. The RBP gene expression was highly heterogeneous; there were significant differences in some cell types, such as keratinocytes, Langerhans, and melanocytes, while there were no significant differences in other cells, such as T cells and fibroblasts, in the two groups. The melanocyte-specific RBP genes were enriched in the apoptosis and immune-related pathways in the patients with vitiligo. Combined with the bulk RNA-seq data of melanocytes, key RBP genes related to melanocytes were identified, including eight upregulated RBP genes (CDKN2A, HLA-A, RPL12, RPL29, RPL31, RPS19, RPS21, and RPS28) and one downregulated RBP gene (SLC3A2). Cell experiments were conducted to explore the role of the key RBP gene SLC3A2 in vitiligo. Cell experiments confirmed that melanocyte proliferation decreased, whereas apoptosis increased, after SLC3A2 knockdown. SLC3A2 knockdown in melanocytes also decreased the SOD activity and melanin content; increased the Fe2+, ROS, and MDA content; significantly increased the expression levels of TYR and COX2; and decreased the expression levels of glutathione and GPX4. Conclusion We identified the RBP genes of different cell subsets in patients with vitiligo and confirmed that downregulating SLC3A2 can promote ferroptosis in melanocytes. These findings provide new insights into the pathogenesis of vitiligo.

show abstract

Evaluation of serum and tissue levels of cold-inducible RNA-binding protein in non-segmental Vitiligo

Cited by 2 publications

References 27 publications

Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing

Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing

Identification and validation of RNA-binding protein SLC3A2 regulates melanocyte ferroptosis in vitiligo by integrated analysis of single-cell and bulk RNA-sequencing

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