Comprehensive Transcriptome Profiling of Balding and Non-Balding Scalps in Trichorhinophalangeal Syndrome Type I Patient
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Trichorhinophalangeal syndrome (TRPS) patients tend to have alopecia that appears to be androgenetic, and this genetic model might give clues to the pathogenesis of hair loss or hair morphogenesis. Objective: This study was conducted to identify additional genetic evidence of TRPS and hair morphogenesis from a TRPS patient. Methods: From one TRPS type I patient, we extracted RNA and profiled whole transcriptome in non-balding and balding scalp areas using high-throughput RNA sequencing. Results: We found a total of 26,320 genes, which comprised 14,892 known genes with new isoforms and 4,883 novel genes from the non-balding and balding areas. Among these, a total of 1,242 genes showed different expression in the two scalp areas (p＜0.05 and log2 fold-change ＞0). Several genes related to the skin and hair, alopecia, and the TRPS1 gene were validated by qRT-PCR. Twelve of 15 genes (KRT6C, KRTAP3-1, MKI67, GPRC5D, TYRP1, DSC1, PMEL, WIF1, SOX21, TINAG, PTGDS, and TRPS1) were down-regulated (10 genes: p＜0.01; SOX21 and PTGDS: p＞0.05), and the three other genes (HBA2, GAL, and DES) were up-regulated (p ＜0.01) in the balding scalp. Many genes related to keratin and hair development were down-regulated in the balding scalp of the TRPS type I patient. In particular, the TRPS1 gene might be related to androgen metabolism and hair morphogenesis. Conclusion: Our result could suggest a novel perspective and evidence to support further study of TRPS and hair morphogenesis.
Abstract
Background: Trichorhinophalangeal syndrome (TRPS) patients tend to have alopecia that appears to be androgenetic, and this genetic model might give clues to the pathogenesis of hair loss or hair morphogenesis. Objective: This study was conducted to identify additional genetic evidence of TRPS and hair morphogenesis from a TRPS patient. Methods: From one TRPS type I patient, we extracted RNA and profiled whole transcriptome in non-balding and balding scalp areas using high-throughput RNA sequencing. Results: We found a total of 26,320 genes, which comprised 14,892 known genes with new isoforms and 4,883 novel genes from the non-balding and balding areas. Among these, a total of 1,242 genes showed different expression in the two scalp areas (p＜0.05 and log2 fold-change ＞0). Several genes related to the skin and hair, alopecia, and the TRPS1 gene were validated by qRT-PCR. Twelve of 15 genes (KRT6C, KRTAP3-1, MKI67, GPRC5D, TYRP1, DSC1, PMEL, WIF1, SOX21, TINAG, PTGDS, and TRPS1) were down-regulated (10 genes: p＜0.01; SOX21 and PTGDS: p＞0.05), and the three other genes (HBA2, GAL, and DES) were up-regulated (p ＜0.01) in the balding scalp. Many genes related to keratin and hair development were down-regulated in the balding scalp of the TRPS type I patient. In particular, the TRPS1 gene might be related to androgen metabolism and hair morphogenesis. Conclusion: Our result could suggest a novel perspective and evidence to support further study of TRPS and hair morphogenesis.
참고문헌 (13)
- Fantauzzo KA, "Trps1 activates a network of secreted Wnt inhibitors and transcription factors crucial to vibrissa follicle morphogenesis", Development, 139, pp.203~214 (2012)
- Shimomura Y, "APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex", Nature, 464, pp.1043~1047 (2010)
- Trapnell C, "Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation", Nat Biotechnol, 28, pp.511~515 (2010)
- Flicek P, "Ensembl 2013", Nucleic Acids Res, 41(Database issue), pp.D48~D55 (2013)
- Anders S, "HTSeq--a Python framework to work with high-throughput sequencing data", Bioinformatics, 31, pp.166~169 (2015)
- Sun J, "TCC: an R package for comparing tag count data with robust normalization strategies", BMC Bioinformatics, 14, pp.219~ (2013)
- Morris RJ, "Capturing and profiling adult hair follicle stem cells", Nat Biotechnol, 22, pp.411~417 (2004)
- Malik TH, "Deletion of the GATA domain of TRPS1 causes an absence of facial hair and provides new insights into the bone disorder in inherited tricho-rhino-phalangeal syndromes", Mol Cell Biol, 22, pp.8592~8600 (2002)
- Gai Z, "The function of TRPS1 in the development and differentiation of bone, kidney, and hair follicles", Histol Histopathol, 26, pp.915~921 (2011)
- Chang GT, "The TRPS1 transcription factor: androgenic regulation in prostate cancer and high expression in breast cancer", Endocr Relat Cancer, 11, pp.815~822 (2004)
- Gao Y, "Comparative transcriptome analysis of fetal skin reveals key genes related to hair follicle morphogenesis in cashmere goats", PLoS One, 11, pp.e0151118~ (2016)
- Kiso M, "The disruption of Sox21-mediated hair shaft cuticle differentiation causes cyclic alopecia in mice", Proc Natl Acad Sci U S A, 106, pp.9292~9297 (2009)
- Garza LA, "Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia", Sci Transl Med, 4, pp.126ra34~ (2012)