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Volume 27
Issue 13
10.3390/ijms27135750
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

FOXP2+ Chief Cells and CXCL14+ Fibroblasts Drive Fibrotic Remodeling in Carotid Body Tumors

by
Kangxi Cao
,
Jiazhi Yu
,
Guangnan Ao
,
Zongli Han
,
Zhongzheng Wang
,
Yunfeng Han
and
Tao Wang
*
Department of Neurosurgery, Peking University Third Hospital, Beijing 100191, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(13), 5750; https://doi.org/10.3390/ijms27135750 (registering DOI)
Submission received: 22 April 2026 / Revised: 14 June 2026 / Accepted: 23 June 2026 / Published: 25 June 2026
(This article belongs to the Collection Advances in Cell and Molecular Biology)
Versions Notes

Abstract

Carotid body tumors (CBTs) exhibit pronounced clinical heterogeneity, particularly in fibrotic progression, yet the underlying cellular mechanisms remain poorly defined. Here, we performed single-cell RNA sequencing on 64,944 cells from three fibrotic CBT (FCBT) and three non-fibrotic CBT (nFCBT) specimens to construct a high-resolution cellular atlas of CBT fibrosis. Integrated analyses revealed that FCBTs are distinguished by a FOXP2+ chief cell subpopulation exhibiting a metabolic shift toward mitochondrial respiration and enhanced MIF signaling, which may facilitate macrophage recruitment. Endothelial cells expanded in FCBTs and acquired pro-angiogenic signatures driven by macrophage-derived CXCL signaling. Notably, CXCL14+ fibroblasts emerged as the principal effectors of extracellular matrix deposition, with lineage inference suggesting their origin from smooth muscle cells. Immune cells, including T/NK and mast cells, further modulated the fibrotic niche through cytokine interactions. This study provides the first comprehensive single-cell dissection of CBT fibrosis, identifies FOXP2+ chief cells as initiators of stromal remodeling, and highlights CXCL14+ fibroblasts as key matrix-producing effectors. These findings nominate FOXP2 and CXCL14 as potential therapeutic targets for mitigating fibrosis in CBT patients.
Keywords: carotid body tumor; fibrosis; single-cell RNA sequencing; FOXP2; CXCL14; tumor microenvironment carotid body tumor; fibrosis; single-cell RNA sequencing; FOXP2; CXCL14; tumor microenvironment

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MDPI and ACS Style

Cao, K.; Yu, J.; Ao, G.; Han, Z.; Wang, Z.; Han, Y.; Wang, T. FOXP2+ Chief Cells and CXCL14+ Fibroblasts Drive Fibrotic Remodeling in Carotid Body Tumors. Int. J. Mol. Sci. 2026, 27, 5750. https://doi.org/10.3390/ijms27135750

AMA Style

Cao K, Yu J, Ao G, Han Z, Wang Z, Han Y, Wang T. FOXP2+ Chief Cells and CXCL14+ Fibroblasts Drive Fibrotic Remodeling in Carotid Body Tumors. International Journal of Molecular Sciences. 2026; 27(13):5750. https://doi.org/10.3390/ijms27135750

Chicago/Turabian Style

Cao, Kangxi, Jiazhi Yu, Guangnan Ao, Zongli Han, Zhongzheng Wang, Yunfeng Han, and Tao Wang. 2026. "FOXP2+ Chief Cells and CXCL14+ Fibroblasts Drive Fibrotic Remodeling in Carotid Body Tumors" International Journal of Molecular Sciences 27, no. 13: 5750. https://doi.org/10.3390/ijms27135750

APA Style

Cao, K., Yu, J., Ao, G., Han, Z., Wang, Z., Han, Y., & Wang, T. (2026). FOXP2+ Chief Cells and CXCL14+ Fibroblasts Drive Fibrotic Remodeling in Carotid Body Tumors. International Journal of Molecular Sciences, 27(13), 5750. https://doi.org/10.3390/ijms27135750

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