title: Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia.
abstract: Androgenetic alopecia (AGA) is a common heritable and androgen-dependent hair loss condition in men. Twelve genetic risk loci are known to date, but it is unclear which genes at these loci are relevant for AGA. Dermal papilla cells (DPCs) located in the hair bulb are the main site of androgen activity in the hair follicle. Widely used monolayer-cultured primary DPCs in hair-related studies often lack dermal papilla characteristics. In contrast, immortalized DPCs have high resemblance to intact dermal papilla. We derived immortalized human DPC lines from balding (BAB) and non-balding (BAN) scalp. Both BAB and BAN retained high proportions of dermal papilla signature gene and versican protein expression. We performed expression analysis of BAB and BAN and annotated AGA risk loci with differentially expressed genes. We found evidence for AR but not EDA2R as the candidate gene at the AGA risk locus on chromosome X. Further, our data suggest TWIST1 (twist family basic helix-loop-helix transcription factor 1) and SSPN (sarcospan) to be the functionally relevant AGA genes at the 7p21.1 and 12p12.1 risk loci, respectively. Down-regulated genes in BAB compared to BAN were highly enriched for vasculature-related genes, suggesting that deficiency of DPC from balding scalps in fostering vascularization around the hair follicle may contribute to the development of AGA.
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Elaine G Y
authors.initials: EGY
authors.lastname: Chew
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Joanna H J
authors.initials: JHJ
authors.lastname: Tan
authors.affiliation: Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London Queen Mary's School of Medicine and Dentistry, Queen Mary College, London, UK.
authors.forename: Adiam W
authors.initials: AW
authors.lastname: Bahta
authors.affiliation: Experimental Dermatology Group, Institute of Medical Biology, Singapore, Singapore.
authors.forename: Bryan S-Y
authors.initials: BS
authors.lastname: Ho
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Xingliang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Cell and Tissue Engineering, Institute of Bioengineering and Nanotechnology, Singapore, Singapore.
authors.forename: Tze Chiun
authors.initials: TC
authors.lastname: Lim
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Yee Yen
authors.initials: YY
authors.lastname: Sia
authors.affiliation: Experimental Dermatology Group, Institute of Medical Biology, Singapore, Singapore; National University of Singapore, YLL School of Medicine, Singapore, Singapore; Department of Medicine, National University Hospital, Singapore, Singapore.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Bigliardi
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Heilmann
authors.affiliation: Cell and Tissue Engineering, Institute of Bioengineering and Nanotechnology, Singapore, Singapore.
authors.forename: Andrew C A
authors.initials: ACA
authors.lastname: Wan
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.affiliation: Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and The London Queen Mary's School of Medicine and Dentistry, Queen Mary College, London, UK.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Philpott
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore. Electronic address: hillmer@gis.a-star.edu.sg.
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
mesh_terms: D000505:Alopecia / Q000235:genetics*; D000728:Androgens / Q000378:metabolism; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016000:Cluster Analysis; D020405:Dermis / Q000166:cytology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D011944:Receptors, Androgen / Q000235:genetics; D012535:Scalp; D012867:Skin / Q000166:cytology*; D051879:Twist-Related Protein 1 / Q000235:genetics; D053340:Xedar Receptor
chemical_list: C410798:AR protein, human; D000728:Androgens; D002352:Carrier Proteins; C506011:EDA2R protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011944:Receptors, Androgen; C109646:SSPN protein, human; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D053340:Xedar Receptor