Localizing Hormone Receptor Expression to Cellular Compartments in Idiopathic Subglottic Stenosis.
Localizing Hormone Receptor Expression to Cellular Compartments in Idiopathic Subglottic Stenosis.
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将激素受体表达定位于特发性声门下狭窄的细胞区室。
DOI：
10.1002/lary.30856
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Gelbard,Alexander
中科院分区：
文献类型：
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作者：
Talatala,EdwardRyanR;Clark,Evan;Ye,Wenda;Davis,RuthJ;Hillel,AlexanderT;Collins,SamuelL;Ramirez-Solano,Marisol;Sheng,Quanhu;Gelbard,Alexander
目的：特发性声门下狭窄（idiopathic subglottic stenosis，iSGS）是一种原因不明的进行性上气道纤维化. iSGS几乎只影响女性;因此，女性激素（雌激素和孕激素）已被提出参与iSGS的发病机制。我们的目的是定位雌激素受体的细胞特异性基因表达，（ESR 1和ESR 2）和孕酮受体（PGR）使用已建立的iSGS单细胞RNA测序（scRNAseq）细胞图谱研究DesignEx对来自iSGS患者的气道瘢痕和健康粘膜的活体分子研究方法建立的scRNAseq图谱由25个，对来自iSGS患者的声门下瘢痕（n= 7）或匹配的未受影响粘膜（n= 3）的974个单独测序的细胞进行ESR 1、ESR 2和PCR的RNA表达的询问。对结果进行定量并在细胞亚群之间进行比较，然后使用均匀流形近似和投影（UMAP）进行可视化。iSGS患者（n= 5）的成纤维细胞内分泌受体的炎症蛋白质评估进行通过流式细胞术。结果在iSGS患者的近端气道粘膜表现出差异表达的内分泌受体（ESR 1，ESR 2，PGR）。在气道瘢痕内，内分泌受体主要由成纤维细胞、免疫细胞和内皮细胞表达。成纤维细胞显示出强烈的ESR 1和PGR表达，而免疫细胞具有ESR 1和ESR 2的RNA。内皮细胞主要表达ESR 2。在未受影响的粘膜上皮细胞表达所有三种受体，这都是减少在气道scarc.ConclusionsscRNAseq数据本地化的内分泌受体表达的特定细胞亚群。这些结果为将来研究激素依赖性机制如何促进、维持或参与iSGS疾病发病机制提供了基础。证据水平NA;基础科学喉镜，133：3506-3511，2023
ObjectivesIdiopathic subglottic stenosis (iSGS) is an unexplained progressive fibrosis of the upper airway. iSGS almost exclusively affects women; as a result, female hormones (estrogen and progesterone) have been proposed to participate in the pathogenesis of iSGS. Our aim was to localize cell‐specific gene expression of estrogen receptors (ESR1andESR2) and progesterone receptor (PGR) using an established iSGS single‐cell RNA sequencing (scRNAseq) cell atlas.Study DesignEx vivomolecular study of airway scar and healthy mucosa from iSGS patients.MethodsAn established scRNAseq atlas consisting of 25,974 individually sequenced cells from subglottic scar (n= 7) or matched unaffected mucosa (n= 3) in iSGS patients was interrogated for RNA expression ofESR1,ESR2, andPGR. Results were quantified and compared across cell subsets, then visualized using Uniform Manifold Approximation and Projection (UMAP). Confirmatory protein assessment of endocrine receptors in fibroblasts from iSGS patients (n= 5) was performed via flow cytometry.ResultsThe proximal airway mucosa in iSGS patients demonstrates differential expression of endocrine receptors (ESR1,ESR2,PGR). Within airway scar, endocrine receptors are primarily expressed by fibroblasts, immune cells, and endothelial cells. Fibroblasts show strongESR1andPGRexpression, while immune cells possess RNA for bothESR1andESR2. Endothelial cells predominantly expressESR2. Epithelial cells in unaffected mucosa express all three receptors, which are all reduced in airway scar.ConclusionsscRNAseq data localized endocrine receptor expression to specific cell subsets. These results provide the foundation for future work interrogating how hormone‐dependent mechanisms promote, sustain, or participate in iSGS disease pathogenesis.Level of EvidenceNA; Basic scienceLaryngoscope, 133:3506–3511, 2023