Molecular characterization of onychomatricoma: Spatial profiling reveals the role of onychofibroblasts in its pathogenesis
Joonho Shim
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Search for more papers by this authorJihye Park
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Search for more papers by this authorYeon Joo Jung
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Search for more papers by this authorKee-Taek Jang
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Search for more papers by this authorEun Ji Kwon
Department of Dermatology, Columbia University Irving Medical Center, New York City, New York, USA
Search for more papers by this authorJong Hee Lee
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Department of Medical Device Management & Research, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea
Search for more papers by this authorCorresponding Author
Dongyoun Lee
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence
Dongyoun Lee, Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea.
Email: [email protected]
Search for more papers by this authorJoonho Shim
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Search for more papers by this authorJihye Park
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Search for more papers by this authorYeon Joo Jung
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Search for more papers by this authorKee-Taek Jang
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Search for more papers by this authorEun Ji Kwon
Department of Dermatology, Columbia University Irving Medical Center, New York City, New York, USA
Search for more papers by this authorJong Hee Lee
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Department of Medical Device Management & Research, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea
Search for more papers by this authorCorresponding Author
Dongyoun Lee
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence
Dongyoun Lee, Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea.
Email: [email protected]
Search for more papers by this authorAbstract
Onychomatricoma (OM) is a rare nail unit tumour with a characteristic presentation of finger-like projections arising from the nail matrix. Due to the lack of transcriptome information, the mechanisms underlying its development are largely unknown. To characterize molecular features involved in the disease pathogenesis, we used digital spatial profiling (DSP) in 2 cases of OM and normal control nail units. Based on the histological evaluation, we selectively profiled 69 regions of interest covering epithelial and stromal compartments of each tissue section. Dermoscopic and histopathologic findings were reviewed in 6 cases. Single-cell RNA sequencing of nail units and DSP were combined to define cell type contributions of OM. We identified 173 genes upregulated in stromal compartments of OM compared to onychodermis, specialized nail mesenchyme. Gene ontology analysis of the upregulated genes suggested the role of Wnt pathway activation in OM pathogenesis. We also found PLA2G2A, a known modulator of Wnt signalling, is strongly and specifically expressed in the OM stroma. The potential role of Wnt pathway was further supported by strong nuclear localization of β-catenin in OM. Compared to the nail matrix epithelium, only a few genes were increased in OM epithelium. Deconvolution of nail unit cell types showed that onychofibroblasts are the dominant cell type in OM stroma. Altogether, integrated spatial and single-cell multi-omics concluded that OM is a tumour that derives a significant proportion of its origin from onychofibroblasts and is associated with upregulation of Wnt signals, which play a key role in the disease pathogenesis.
CONFLICT OF INTEREST
The authors declare they have no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
All of the relevant data needed to evaluate the findings in the paper are publicly available and sequencing data of the polydactyly scRNA-seq have been deposited in the Gene Expression Omnibus (GEO) under accession code GSE158970. The GeoMX DSP transcript are provided in File S1.
Supporting Information
| Filename | Description |
|---|---|
| exd14736-sup-0001-FigureS1.pdfPDF document, 2.4 MB |
Figure S1. Digital spatial gene expression profiling of the selected ROIs. (A) Violin plot representing probe count detected by each ROI. (B) Violin plot depicting normalized count value by each ROIs. Trimmed mean of M-values (TMM) methods, the normalization method implemented in the edgeR package, was employed to obtain normalized count value. ROI, region of interest; OM, onychomatricoma; ADN, adjacent normal dermis; NME, nail matrix epithelium; NBE, nail bed epithelium; PNF, proximal nail fold; OD, onychodermis. |
| exd14736-sup-0002-FigureS2.pdfPDF document, 1.8 MB |
Figure S2. Volcano plots representing differentially expressed genes enriched in the adult nail unit ROIs. (A) Volcano plots representing differentially expressed genes between onychodermis ROIs and control dermis ROIs. (B) Volcano plot of nail matrix epithelium ROIs. NME, nail matrix epithelium; PNF, proximal nail fold; OD, onychodermis |
| exd14736-sup-0003-FigureS3.pdfPDF document, 520.7 KB |
Figure S3. Boxplots depicting the expression level of PLA2G2A and RSPO4 in the stromal ROIs. OM, onychomatricoma; ADN, adjacent normal dermis; PNF, proximal nail fold; OD, onychodermis. |
| exd14736-sup-0004-TableS1.docxWord 2007 document , 18.8 KB |
Table S1. Summary of clinical, dermoscopic, and histologic findings of individual patients with onychomatricoma. |
| exd14736-sup-0005-TableS2.docxWord 2007 document , 18.3 KB |
Table S2. Histological features of the selected ROIs. |
| exd14736-sup-0006-TableS3.docxWord 2007 document , 28.4 KB |
Table S3. Summary of sequencing quality of the selected ROIs. |
| exd14736-sup-0007-AppendixS1.xlsExcel spreadsheet, 8.7 MB |
Table S4. List of differentially expressed genes in onychomatricoma stromal ROIs versus control dermis ROIs. Table S5. List of differentially expressed genes in onychomatricoma epithelial ROIs versus control epidermis ROIs. Table S6. List of differentially expressed genes in onychomatricoma stromal ROIs versus onychodermis ROIs. Table S7. List of differentially expressed genes in onychomatricoma epithelial ROIs versus nail matrix epidermis ROIs. File S1. The NanoString GeoMX DSP data for the 69 selected ROIs. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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