title: Biomarker Discovery by Modeling Behçet's Disease with Patient-Specific Human Induced Pluripotent Stem Cells.
abstract: Behçet's disease (BD) is a chronic inflammatory and multisystemic autoimmune disease of unknown etiology. Due to the lack of a specific test for BD, its diagnosis is very difficult and therapeutic options are limited. Induced pluripotent stem cell (iPSC) technology, which provides inaccessible disease-relevant cell types, opens a new era for disease treatment. In this study, we generated BD iPSCs from patient somatic cells and differentiated them into hematopoietic precursor cells (BD iPSC-HPCs) as BD model cells. Based on comparative transcriptome analysis using our BD model cells, we identified eight novel BD-specific genes, AGTR2, CA9, CD44, CXCL1, HTN3, IL-2, PTGER4, and TSLP, which were differentially expressed in BD patients compared with healthy controls or patients with other immune diseases. The use of CXCL1 as a BD biomarker was further validated at the protein level using both a BD iPSC-HPC-based assay system and BD patient serum samples. Furthermore, we show that our BD iPSC-HPC-based drug screening system is highly effective for testing CXCL1 BD biomarkers, as determined by monitoring the efficacy of existing anti-inflammatory drugs. Our results shed new light on the usefulness of patient-specific iPSC technology in the development of a benchmarking platform for disease-specific biomarkers, phenotype- or target-driven drug discovery, and patient-tailored therapies.
authors.affiliation: 1 Stem Cell Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon, Republic of Korea.|2 Department of Functional Genomics, University of Science and Technology , Daejeon, Republic of Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Son
authors.affiliation: 3 Stem Cell Research Laboratory, Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon, Republic of Korea.
authors.forename: Young-Dae
authors.initials: YD
authors.lastname: Kim
authors.affiliation: 3 Stem Cell Research Laboratory, Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon, Republic of Korea.
authors.forename: Binna
authors.initials: B
authors.lastname: Seol
authors.affiliation: 3 Stem Cell Research Laboratory, Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon, Republic of Korea.
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Lee
authors.affiliation: 3 Stem Cell Research Laboratory, Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon, Republic of Korea.
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Na
authors.affiliation: 4 Department of Rheumatology, University of Ulsan College of Medicine , Seoul, Republic of Korea.
authors.forename: Bin
authors.initials: B
authors.lastname: Yoo
authors.affiliation: 5 Department of Orthopedic Surgery, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Republic of Korea.
authors.forename: Jae-Suk
authors.initials: JS
authors.lastname: Chang
authors.affiliation: 2 Department of Functional Genomics, University of Science and Technology , Daejeon, Republic of Korea.|3 Stem Cell Research Laboratory, Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon, Republic of Korea.
authors.forename: Yee Sook
authors.initials: YS
authors.lastname: Cho
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation; D054360:Chemokine CXCL1 / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015203:Reproducibility of Results; D059467:Transcriptome / Q000235:genetics
chemical_list: D015415:Biomarkers; D054360:Chemokine CXCL1
keywords: Behçet's disease; CXCL1; biomarker; drug discovery; hematopoietic precursor cells; induced pluripotent stem cells