RNA-seq and flow-cytometry of conventional, scalp, and palmoplantar psoriasis reveal shared and distinct molecular pathways.
Richard Ahn, Di Yan, Hsin-Wen Chang, Kristina Lee, Shrishti Bhattarai, Zhi-Ming Huang, Mio Nakamura, Rasnik Singh, Ladan Afifi, Keyon Taravati, Priscila Munoz-Sandoval, Mariela Pauli, Michael D Rosenblum, Wilson Liao
Author Information
- Richard Ahn: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States. richardahn@ucla.edu. ORCID
- Di Yan: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Hsin-Wen Chang: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Kristina Lee: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Shrishti Bhattarai: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Zhi-Ming Huang: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Mio Nakamura: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Rasnik Singh: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Ladan Afifi: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Keyon Taravati: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Priscila Munoz-Sandoval: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Mariela Pauli: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Michael D Rosenblum: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States.
- Wilson Liao: Department of Dermatology, University of California, San Francisco, San Francisco, CA, United States. ORCID
It has long been recognized that anatomic location is an important feature for defining distinct subtypes of plaque psoriasis. However, little is known about the molecular differences between scalp, palmoplantar, and conventional plaque psoriasis. To investigate the molecular heterogeneity of these psoriasis subtypes, we performed RNA-seq and flow cytometry on skin samples from individuals with scalp, palmoplantar, and conventional plaque psoriasis, along with samples from healthy control patients. We performed differential expression analysis and network analysis using weighted gene coexpression network analysis (WGCNA). Our analysis revealed a core set of 763 differentially expressed genes common to all sub-types of psoriasis. In contrast, we identified 605, 632, and 262 genes uniquely differentially expressed in conventional, scalp, and palmoplantar psoriasis, respectively. WGCNA and pathway analysis revealed biological processes for the core genes as well as subtype-specific genes. Flow cytometry analysis revealed a shared increase in the percentage of CD4+ T regulatory cells in all psoriasis subtypes relative to controls, whereas distinct psoriasis subtypes displayed differences in IL-17A, IFN-gamma, and IL-22 production. This work reveals the molecular heterogeneity of plaque psoriasis and identifies subtype-specific signaling pathways that will aid in the development of therapy that is appropriate for each subtype of plaque psoriasis.
Adult
Aged
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cluster Analysis
Cytokines
Female
Flow Cytometry
Gene Expression Profiling
Gene Regulatory Networks
Humans
Male
Middle Aged
Principal Component Analysis
Psoriasis
Scalp
Sequence Analysis, RNA
Signal Transduction
Transcriptome