Digital spatial profiling of human parathyroid tumors reveals cellular and molecular alterations linked to vitamin D deficiency.
Digital spatial profiling of human parathyroid tumors reveals cellular and molecular alterations linked to vitamin D deficiency.
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人甲状旁腺肿瘤的数字空间分析揭示了与维生素D缺乏有关的细胞和分子改变。
DOI：
10.1093/pnasnexus/pgad073
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发表时间：
2023-03
期刊：
影响因子：
--
通讯作者：
Koh, James
中科院分区：
文献类型：
--
作者：
Tu, Chia-Ling;Chang, Wenhan;Sosa, Julie A.;Koh, James
原发性甲状旁腺功能亢进（PHPT）是一种常见的内分泌肿瘤性疾病，其特征是继发于甲状旁腺激素（PTH）分泌不适当升高的钙稳态破坏。PHPT患者血清25-羟基维生素D（25 OHD）水平较低的情况明显多于一般人群（1-3），但这种相关性的基础尚不清楚。我们采用了一种空间上定义的原位全转录组学和选择性蛋白质组学分析方法，比较维生素D缺乏或维生素D充足的PHPT患者甲状旁腺腺瘤的基因表达模式和细胞组成。作为正常组织对照，平行检查了正常血糖尸体供体甲状旁腺的横断面。在这里，我们报告说，甲状旁腺肿瘤从维生素D缺乏PHPT患者（Def-Ts）是本质上不同的维生素D-充满患者（Rep-Ts）相似的年龄和术前临床表现。Def-Ts中甲状旁腺嗜酸性细胞含量（47.8%）明显高于Rep-Ts（17.8%）和正常供者腺体（7.7%）。维生素D缺乏与电子传递链和氧化磷酸化途径组分的表达增加有关。甲状旁腺嗜酸细胞，而形态上不同的，是可比的主细胞在转录水平上，和维生素D缺乏症的影响，这两种细胞类型的转录谱以类似的方式。这些数据表明，嗜酸性细胞来自主细胞，并暗示其丰度增加可能是由低维生素D状态引起的。基因集富集分析表明，Def-Ts中改变的途径与Rep-Ts不同，表明这些组中存在替代肿瘤病因。因此，嗜酸性粒细胞含量增加可能是肿瘤易感细胞应激的形态学指标。
Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population (1–3), but the basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from vitamin D-deficient or vitamin D-replete PHPT patients. A cross-sectional panel of eucalcemic cadaveric donor parathyroid glands was examined in parallel as normal tissue controls. Here, we report that parathyroid tumors from vitamin D-deficient PHPT patients (Def-Ts) are intrinsically different from those of vitamin D-replete patients (Rep-Ts) of similar age and preoperative clinical presentation. The parathyroid oxyphil cell content is markedly higher in Def-Ts (47.8%) relative to Rep-Ts (17.8%) and normal donor glands (7.7%). Vitamin D deficiency is associated with increased expression of electron transport chain and oxidative phosphorylation pathway components. Parathyroid oxyphil cells, while morphologically distinct, are comparable to chief cells at the transcriptional level, and vitamin D deficiency affects the transcriptional profiles of both cell types in a similar manner. These data suggest that oxyphil cells are derived from chief cells and imply that their increased abundance may be induced by low vitamin D status. Gene set enrichment analysis reveals that pathways altered in Def-Ts are distinct from Rep-Ts, suggesting alternative tumor etiologies in these groups. Increased oxyphil content may thus be a morphological indicator of tumor-predisposing cellular stress.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
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作者：
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通讯作者：
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影响因子：
3.3
作者：
BEDETTI, CD;DEKKER, A;WATSON, CG
通讯作者：
WATSON, CG
影响因子：
2.7
作者：
Costa-Guda J;Tokura T;Roth SI;Arnold A
通讯作者：
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