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解析自身免疫性甲状腺疾病的分子结构在空间分辨率。

Unraveling the molecular architecture of autoimmune thyroid diseases at spatial resolution.

机构信息

Department of Endocrinology and Nutrition Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER GCV14/ER/12), Madrid, Spain.

Department of General and Digestive Surgery, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa, Universidad Autónoma de Madrid, Madrid, Spain.

出版信息

Nat Commun. 2024 Jul 13;15(1):5895. doi: 10.1038/s41467-024-50192-5.

DOI:10.1038/s41467-024-50192-5
PMID:39003267
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11246508/
Abstract

Autoimmune thyroid diseases (AITD) such as Graves' disease (GD) or Hashimoto's thyroiditis (HT) are organ-specific diseases that involve complex interactions between distinct components of thyroid tissue. Here, we use spatial transcriptomics to explore the molecular architecture, heterogeneity and location of different cells present in the thyroid tissue, including thyroid follicular cells (TFCs), stromal cells such as fibroblasts, endothelial cells, and thyroid infiltrating lymphocytes. We identify damaged antigen-presenting TFCs with upregulated CD74 and MIF expression in thyroid samples from AITD patients. Furthermore, we discern two main fibroblast subpopulations in the connective tissue including ADIRF myofibroblasts, mainly enriched in GD, and inflammatory fibroblasts, enriched in HT patients. We also demonstrate an increase of fenestrated PLVAP vessels in AITD, especially in GD. Our data unveil stromal and thyroid epithelial cell subpopulations that could play a role in the pathogenesis of AITD.

摘要

自身免疫性甲状腺疾病(AITD),如格雷夫斯病(GD)或桥本甲状腺炎(HT),是涉及甲状腺组织中不同成分之间复杂相互作用的器官特异性疾病。在这里,我们使用空间转录组学来探索甲状腺组织中不同细胞的分子结构、异质性和位置,包括甲状腺滤泡细胞(TFCs)、基质细胞(如成纤维细胞)、内皮细胞和甲状腺浸润淋巴细胞。我们在 AITD 患者的甲状腺样本中发现了表达上调的 CD74 和 MIF 的受损抗原呈递 TFCs。此外,我们在结缔组织中辨别出两种主要的成纤维细胞亚群,包括主要在 GD 中富集的 ADIRF 肌成纤维细胞和在 HT 患者中富集的炎症成纤维细胞。我们还证明 AITD 中窗孔性 PLVAP 血管增加,尤其是在 GD 中。我们的数据揭示了可能在 AITD 发病机制中起作用的基质和成甲状腺上皮细胞亚群。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/30350e0be67b/41467_2024_50192_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/a1f7cc1f0d47/41467_2024_50192_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/f739c5722749/41467_2024_50192_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/6a8eb65af6a1/41467_2024_50192_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/d30dabd15329/41467_2024_50192_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/1c00d4cb71c4/41467_2024_50192_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/f2d2deb553d6/41467_2024_50192_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/bd9bcae54a5b/41467_2024_50192_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/30350e0be67b/41467_2024_50192_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/a1f7cc1f0d47/41467_2024_50192_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/f739c5722749/41467_2024_50192_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/6a8eb65af6a1/41467_2024_50192_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/d30dabd15329/41467_2024_50192_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/1c00d4cb71c4/41467_2024_50192_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/f2d2deb553d6/41467_2024_50192_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/bd9bcae54a5b/41467_2024_50192_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ce/11246508/30350e0be67b/41467_2024_50192_Fig8_HTML.jpg

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