{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:31:47Z","timestamp":1792171907415,"version":"4.4.0"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T00:00:00Z","timestamp":1735171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI)","award":["RS-2024-00351858"],"award-info":[{"award-number":["RS-2024-00351858"]}]},{"name":"Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI)","award":["23C0125L1"],"award-info":[{"award-number":["23C0125L1"]}]},{"name":"Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute (KHIDI)","award":["24D0102L1"],"award-info":[{"award-number":["24D0102L1"]}]},{"name":"the Ministry of Health &amp; Welfare, Republic of Korea","award":["RS-2024-00351858"],"award-info":[{"award-number":["RS-2024-00351858"]}]},{"name":"the Ministry of Health &amp; Welfare, Republic of Korea","award":["23C0125L1"],"award-info":[{"award-number":["23C0125L1"]}]},{"name":"the Ministry of Health &amp; Welfare, Republic of Korea","award":["24D0102L1"],"award-info":[{"award-number":["24D0102L1"]}]},{"name":"Korean Fund for Regenerative Medicine funded by Ministry of Science and ICT, and Ministry of Health and Welfare, Republic of Korea","award":["RS-2024-00351858"],"award-info":[{"award-number":["RS-2024-00351858"]}]},{"name":"Korean Fund for Regenerative Medicine funded by Ministry of Science and ICT, and Ministry of Health and Welfare, Republic of Korea","award":["23C0125L1"],"award-info":[{"award-number":["23C0125L1"]}]},{"name":"Korean Fund for Regenerative Medicine funded by Ministry of Science and ICT, and Ministry of Health and Welfare, Republic of Korea","award":["24D0102L1"],"award-info":[{"award-number":["24D0102L1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We previously demonstrated that C-X-C Motif Chemokine Ligand 12 (CXCL12) is primarily secreted by dermal fibroblasts in response to androgens and induces hair miniaturization in the mouse androgenic alopecia (AGA) model. However, the direct effects of androgen-induced CXCL12 on dermal papilla cells (DPCs) and dermal sheath cup cells (DSCs) have not been demonstrated. First, we compared single-cell RNA sequencing data between mouse and human skin, and the results show that CXCL12 is highly co-expressed with the androgen receptor (AR) in the DPCs and DSCs of only human hair. Immunohistochemistry also showed that CXCL12 is co-expressed with the AR in the DPCs and DSCs of human hair follicles. In human hair organ culture, androgens also increased CXCL12 expression in DPCs and DSCs and reduced hair length, while the CXCL12 antibody increased hair length via AR inactivation. CXCL12 mRNA was upregulated by androgen treatment in primary human DPCs and DSCs. On the contrary, AR inhibitors or siRNA treatment reduced CXCL12 expression. Collectively, these results suggest that CXCL12 is co-expressed with the AR in the DPCs and DSCs of human hair follicles; therefore, inhibition of CXCL12 using antibodies is a promising strategy for AGA treatment.<\/jats:p>","DOI":"10.3390\/ijms26010095","type":"journal-article","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T03:10:49Z","timestamp":1735182649000},"page":"95","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Differential Expression of CXCL12 in Human and Mouse Hair: Androgens Induce CXCL12 in Human Dermal Papilla and Dermal Sheath Cup"],"prefix":"10.3390","volume":"26","author":[{"given":"Mei","family":"Zheng","sequence":"first","affiliation":[{"name":"Epi Biotech Co., Ltd., Incheon 21983, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5840-8987","authenticated-orcid":false,"given":"Seungchan","family":"An","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In Guk","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jino","family":"Kim","sequence":"additional","affiliation":[{"name":"New Hair Institute, Seoul 06134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Serk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4020-5372","authenticated-orcid":false,"given":"Minsoo","family":"Noh","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hyuk","family":"Sung","sequence":"additional","affiliation":[{"name":"Epi Biotech Co., Ltd., Incheon 21983, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e337","DOI":"10.1016\/j.clgc.2019.11.004","article-title":"Effect of CXCL12 and Its Receptors on Unpredictable Renal Cell Carcinoma","volume":"18","author":"Floranovic","year":"2020","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cytogfr.2018.10.004","article-title":"Pathological roles of the homeostatic chemokine CXCL12","volume":"44","author":"Janssens","year":"2018","journal-title":"Cytokine Growth Factor. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41586-024-08002-x","article-title":"A prenatal skin atlas reveals immune regulation of human skin morphogenesis","volume":"635","author":"Gopee","year":"2024","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/exd.12523","article-title":"Cxcr4 is transiently expressed in both epithelial and mesenchymal compartments of nascent hair follicles but is not required for follicle formation","volume":"23","author":"Sennett","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zheng, M., Oh, S.H., Choi, N., Choi, Y.J., Kim, J., and Sung, J.H. (2022). CXCL12 inhibits hair growth through CXCR4. Biomed. Pharmacother., 150.","DOI":"10.1016\/j.biopha.2022.112996"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jdermsci.2020.09.001","article-title":"Pro-inflammatory Vdelta1(+)T-cells infiltrates are present in and around the hair bulbs of non-lesional and lesional alopecia areata hair follicles","volume":"100","author":"Uchida","year":"2020","journal-title":"J. Dermatol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zheng, M., Kim, M.H., Park, S.G., Kim, W.S., Oh, S.H., and Sung, J.H. (2024). CXCL12 Neutralizing Antibody Promotes Hair Growth in Androgenic Alopecia and Alopecia Areata. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031705"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"An, S., Zheng, M., Park, I.G., Park, S.G., Noh, M., and Sung, J.H. (2024). Humanized CXCL12 antibody delays onset and modulates immune response in alopecia areata mice: Insights from single-cell RNA sequencing. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1444777"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.stem.2020.01.012","article-title":"The Molecular Anatomy of Mouse Skin during Hair Growth and Rest","volume":"26","author":"Joost","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.jcjd.2016.03.004","article-title":"Testosterone and Voluntary Exercise Promote Angiogenesis in Hearts of Rats with Diabetes by Enhancing Expression of VEGF-A and SDF-1a","volume":"40","author":"Chodari","year":"2016","journal-title":"Can. J. Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ejphar.2012.03.032","article-title":"Testosterone replacement therapy promotes angiogenesis after acute myocardial infarction by enhancing expression of cytokines HIF-1a, SDF-1a and VEGF","volume":"684","author":"Chen","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1159\/000484584","article-title":"Androgen Triggers the Pro-Migratory CXCL12\/CXCR4 Axis in AR-Positive Breast Cancer Cell Lines: Underlying Mechanism and Possible Implications for the Use of Aromatase Inhibitors in Breast Cancer","volume":"44","author":"Azariadis","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/sj.jid.5700069","article-title":"Involvement of the CXCL12\/CXCR4 pathway in the recovery of skin following burns","volume":"126","author":"Avniel","year":"2006","journal-title":"J. Investig. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S98","DOI":"10.1016\/0923-1811(94)90040-X","article-title":"Mechanism of action of androgen in hair follicles","volume":"7","author":"Itami","year":"1994","journal-title":"J. Dermatol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1016\/j.jid.2022.01.003","article-title":"Androgen Receptor-Mediated Paracrine Signaling Induces Regression of Blood Vessels in the Dermal Papilla in Androgenetic Alopecia","volume":"142","author":"Deng","year":"2022","journal-title":"J. Investig. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/sj.jid.5701147","article-title":"Premature senescence of balding dermal papilla cells in vitro is associated with p16(INK4a) expression","volume":"128","author":"Bahta","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.21037\/atm-22-4634","article-title":"Investigation of hub genes and immune infiltration in androgenetic alopecia using bioinformatics analysis","volume":"10","author":"Zhou","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e35242","DOI":"10.1097\/MD.0000000000035242","article-title":"Identification of immune microenvironment changes, immune-related pathways and genes in male androgenetic alopecia","volume":"102","author":"Xiong","year":"2023","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1111\/bjd.15577","article-title":"Study of gene expression alteration in male androgenetic alopecia: Evidence of predominant molecular signalling pathways","volume":"177","author":"Michel","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.jaad.2021.09.040","article-title":"Perifollicular inflammation and follicular spongiosis in androgenetic alopecia","volume":"86","author":"Plante","year":"2022","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1007\/s11095-015-1729-8","article-title":"Internalization, Trafficking, Intracellular Processing and Actions of Antibody-Drug Conjugates","volume":"32","author":"Xu","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s13238-017-0408-4","article-title":"Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins","volume":"9","author":"Liu","year":"2018","journal-title":"Protein Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/s41588-023-01445-4","article-title":"Integrated single-cell chromatin and transcriptomic analyses of human scalp identify gene-regulatory programs and critical cell types for hair and skin diseases","volume":"55","author":"Wang","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive Integration of Single-Cell Data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/imcb.12616","article-title":"Hepatic TREM2(+) macrophages express matrix metalloproteinases to control fibrotic scar formation","volume":"101","author":"Lee","year":"2023","journal-title":"Immunol. Cell Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/95\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:00:21Z","timestamp":1760115621000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/1\/95"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,26]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26010095"],"URL":"https:\/\/doi.org\/10.3390\/ijms26010095","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,26]]}}}