PMID- 38214142 OWN - NLM STAT- MEDLINE DCOM- 20240412 LR - 20240412 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 239 IP - 4 DP - 2024 Apr TI - Single-cell transcriptome analysis reveals tumoral microenvironment heterogenicity and hypervascularization in human carotid body tumor. PG - e31175 LID - 10.1002/jcp.31175 [doi] AB - Carotid body tumor (CBT) is a rare neck tumor located at the adventitia of the common carotid artery bifurcation. The prominent pathological features of CBT are high vascularization and abnormal proliferation. However, single-cell transcriptome analysis of the microenvironment composition and molecular complexity in CBT has yet to be performed. In this study, we performed single-cell RNA sequencing (scRNA-seq) analysis on human CBT to define the cells that contribute to hypervascularization and chronic hyperplasia. Unbiased clustering analysis of transcriptional profiles identified 16 distinct cell populations including endothelial cells (ECs), smooth muscle cells (SMCs), neuron cells, macrophage cells, neutrophil cells, and T cells. Within the ECs population, we defined subsets with angiogenic capacity plus clear signs of later endothelial progenitor cells (EPCs) to normal ECs. Two populations of macrophages were detectable in CBT, macrophage1 showed enrichment in hypoxia-inducible factor-1 (HIF-1) and as well as an early EPCs cell-like population expressing CD14 and vascular endothelial growth factor. In addition to HIF-1-related transcriptional protein expression, macrophages1 also display a neovasculogenesis-promoting phenotype. SMCs included three populations showing platelet-derived growth factor receptor beta and vimentin expression, indicative of a cancer-associated fibroblast phenotype. Finally, we identified three types of neuronal cells, including chief cells and sustentacular cells, and elucidated their distinct roles in the pathogenesis of CBT and abnormal proliferation of tumors. Overall, our study provided the first comprehensive characterization of the transcriptional landscape of CBT at scRNA-seq profiles, providing novel insights into the mechanisms underlying its formation. CI - (c) 2024 Wiley Periodicals LLC. FAU - Cai, Gaopo AU - Cai G AUID- ORCID: 0009-0009-2787-4131 AD - Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Hua, Zhaohui AU - Hua Z AD - Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Zhang, Linfeng AU - Zhang L AD - Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Chen, Yutian AU - Chen Y AD - Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Li, Xu AU - Li X AD - Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Ma, Ke AU - Ma K AD - Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Xia, Zongping AU - Xia Z AD - Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Li, Zhen AU - Li Z AD - Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. LA - eng GR - 81873527/National Natural Science Foundation of China/ PT - Journal Article DEP - 20240112 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Humans MH - Single-Cell Gene Expression Analysis MH - *Carotid Body Tumor/pathology MH - Vascular Endothelial Growth Factor A MH - Carotid Arteries/pathology MH - *Endothelial Progenitor Cells MH - Transcriptome/genetics MH - Tumor Microenvironment/genetics MH - Single-Cell Analysis OTO - NOTNLM OT - carotid body tumor OT - hypervascularization OT - microenvironment OT - single cell sequencing EDAT- 2024/01/12 06:42 MHDA- 2024/04/12 06:44 CRDT- 2024/01/12 04:44 PHST- 2023/11/07 00:00 [revised] PHST- 2023/07/18 00:00 [received] PHST- 2023/12/07 00:00 [accepted] PHST- 2024/04/12 06:44 [medline] PHST- 2024/01/12 06:42 [pubmed] PHST- 2024/01/12 04:44 [entrez] AID - 10.1002/jcp.31175 [doi] PST - ppublish SO - J Cell Physiol. 2024 Apr;239(4):e31175. doi: 10.1002/jcp.31175. Epub 2024 Jan 12.