Antlers on does: An unexpected role of macrophages in deer biology

Antlers, a male deer secondary sex characteristic, are unique mammalian appendages that fully regenerate annually, under androgen regulation. Stem cells located in the antlerogenic periosteum (AP), a tissue overlaying the frontal crest of both male and female deer, play a crucial role in antlerogenesis. Nonetheless, the underlying molecular mechanisms as to how antlerogenesis is regulated by androgens remain largely unexplored. Here, we show that androgens regulate antler growth via macrophages. Bulk RNA sequencing revealed a significant enrichment of immune-related factors in the androgen-activated antlerogenic periosteum (AAP), and single-cell RNA sequencing identified a cluster of AAP cells overexpressing macrophage chemokine CCL2. Additionally, the presence of a substantial number of monocytes/macrophages was detected in the skin overlying the AAP. Histological examination confirmed macrophage accumulation in the AAP. Removal of macrophages with clodronate effectively inhibited antler generation in male sika deer as well as in nude mice engrafted with the AP. Furthermore, testosterone up-regulated CCL2 expression in the AP cells (APCs), thus enhancing their chemotactic effect on recruitment of macrophages. Remarkably, female sika deer developed antlers following local injection of CCL2, autologous macrophages, or even immune response inducer lipopolysaccharide (LPS). Therefore, macrophages play an essential role in deer antler generation.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-06-13
DOI
https://doi.org/10.1073/pnas.2424448122
Primary Topic
Single-cell and spatial transcriptomics
Type
article
Field-Weighted Citation Impact
0.00

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article

Antlers on does: An unexpected role of macrophages in deer biology

Jing Ren, Datao Wang, Louis Chonco, Hengxing Ba et al.
Proceedings of the National Academy of Sciences
Single-cell and spatial transcriptomics
article

Antlers on does: An unexpected role of macrophages in deer biology

Jing Ren, Datao Wang, Louis Chonco, Hengxing Ba, Xunsheng Li, Tomás Landete‐Castillejos, Gerry Melino, Guokun Zhang, Yufang Shi, W. Shi, Chao Ma, Zhen Wang, Chunyi Li, Hongmei Sun
article en

Abstract

Antlers, a male deer secondary sex characteristic, are unique mammalian appendages that fully regenerate annually, under androgen regulation. Stem cells located in the antlerogenic periosteum (AP), a tissue overlaying the frontal crest of both male and female deer, play a crucial role in antlerogenesis. Nonetheless, the underlying molecular mechanisms as to how antlerogenesis is regulated by androgens remain largely unexplored. Here, we show that androgens regulate antler growth via macrophages. Bulk RNA sequencing revealed a significant enrichment of immune-related factors in the androgen-activated antlerogenic periosteum (AAP), and single-cell RNA sequencing identified a cluster of AAP cells overexpressing macrophage chemokine CCL2. Additionally, the presence of a substantial number of monocytes/macrophages was detected in the skin overlying the AAP. Histological examination confirmed macrophage accumulation in the AAP. Removal of macrophages with clodronate effectively inhibited antler generation in male sika deer as well as in nude mice engrafted with the AP. Furthermore, testosterone up-regulated CCL2 expression in the AP cells (APCs), thus enhancing their chemotactic effect on recruitment of macrophages. Remarkably, female sika deer developed antlers following local injection of CCL2, autologous macrophages, or even immune response inducer lipopolysaccharide (LPS). Therefore, macrophages play an essential role in deer antler generation.

Proceedings of the National Academy of SciencesVol. 122(24)
University of Rome Tor Vergata (IT), Soochow University (TW), Soochow University (CN), Instituto de Investigación en Recursos Cinegéticos (ES), Second Affiliated Hospital of Soochow University (CN), Chinese Academy of Agricultural Sciences (CN), Jilin Agricultural University (CN), First Affiliated Hospital of Soochow University (CN), Institute of Special Animal and Plant Sciences (CN), The Fourth Affiliated Hospital of Soochow University (Suzhou Dushu Lake Hospital), Changchun University (CN), University of Castilla-La Mancha (ES)
Natural Science Foundation of Jilin Province, National Natural Science Foundation of China, Government of Jiangsu Province, People's Government of Jilin Province, Chinese Academy of Agricultural Sciences, Junta de Comunidades de Castilla-La Mancha
Openalex Percentile: Top 88%
Single-cell and spatial transcriptomics
DOIOpen Access PDFOpenAlex
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