Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

Elaine G.Y. Chew; Joanna H.J. Tan; Adiam W. Bahta; Bryan S.Y. Ho; Xingliang Liu; Tze Chiun Lim; Yee Yen Sia; Paul L. Bigliardi; Stefanie Heilmann; Andrew C.A. Wan; Markus M. Nöthen; Michael P. Philpott; Axel M. Hillmer

doi:10.1016/j.jid.2016.03.032

Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

Elaine G.Y. Chew, Joanna H.J. Tan, Adiam W. Bahta, Bryan S.Y. Ho, Xingliang Liu, Tze Chiun Lim, Yee Yen Sia, Paul L. Bigliardi, Stefanie Heilmann, Andrew C.A. Wan, Markus M. Nöthen, Michael P. Philpott, Axel M. Hillmer

Dermatology

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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.

Original language	English (US)
Pages (from-to)	1559-1567
Number of pages	9
Journal	Journal of Investigative Dermatology
Volume	136
Issue number	8
DOIs	https://doi.org/10.1016/j.jid.2016.03.032
State	Published - Aug 1 2016

Bibliographical note

Funding Information:
We are grateful for the patients who contributed hair follicles to the study. This work was supported by the Agency for Science, Technology and Research (A*STAR). EC is supported by the A*STAR Graduate Scholarship program. The data reported in this paper have been deposited in Gene Expression Omnibus, http://www.ncbi.nlm.nih.gov/geo (GEO Series accession number GSE66663 and GSE66664 ).

Publisher Copyright:
© 2016 The Authors

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Chew, E. G. Y., Tan, J. H. J., Bahta, A. W., Ho, B. S. Y., Liu, X., Lim, T. C., Sia, Y. Y., Bigliardi, P. L., Heilmann, S., Wan, A. C. A., Nöthen, M. M., Philpott, M. P., & Hillmer, A. M. (2016). Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia. Journal of Investigative Dermatology, 136(8), 1559-1567. https://doi.org/10.1016/j.jid.2016.03.032

Chew, EGY, Tan, JHJ, Bahta, AW, Ho, BSY, Liu, X, Lim, TC, Sia, YY, Bigliardi, PL, Heilmann, S, Wan, ACA, Nöthen, MM, Philpott, MP & Hillmer, AM 2016, 'Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia', Journal of Investigative Dermatology, vol. 136, no. 8, pp. 1559-1567. https://doi.org/10.1016/j.jid.2016.03.032

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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.",

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note = "Funding Information: We are grateful for the patients who contributed hair follicles to the study. This work was supported by the Agency for Science, Technology and Research (A*STAR). EC is supported by the A*STAR Graduate Scholarship program. The data reported in this paper have been deposited in Gene Expression Omnibus, http://www.ncbi.nlm.nih.gov/geo (GEO Series accession number GSE66663 and GSE66664 ). Publisher Copyright: {\textcopyright} 2016 The Authors",

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AU - Bahta, Adiam W.

AU - Ho, Bryan S.Y.

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AU - Philpott, Michael P.

AU - Hillmer, Axel M.

N1 - Funding Information: We are grateful for the patients who contributed hair follicles to the study. This work was supported by the Agency for Science, Technology and Research (A*STAR). EC is supported by the A*STAR Graduate Scholarship program. The data reported in this paper have been deposited in Gene Expression Omnibus, http://www.ncbi.nlm.nih.gov/geo (GEO Series accession number GSE66663 and GSE66664 ). Publisher Copyright: © 2016 The Authors

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N2 - 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.

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Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

Abstract

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