Single-cell RNA sequencing in silent corticotroph tumors confirms impaired POMC processing and provides new insights into their invasive behavior.
Single-cell RNA sequencing in silent corticotroph tumors confirms impaired POMC processing and provides new insights into their invasive behavior.
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DOI：
10.1530/eje-21-1183
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发表时间：
2022-05-12
影响因子：
5.8
通讯作者：
Heaney, Anthony P.
中科院分区：
文献类型：
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作者：
Zhang, Dongyun;Hugo, Willy;Bergsneider, Marvin;Wang, Marilene B.;Kim, Won;Vinters, Harry V.;Heaney, Anthony P.
提供对无症状性垂体促肾上腺皮质激素细胞瘤中POMC加工缺陷和侵袭行为的见解。使用单细胞RNAseq比较沉默和活动性促肾上腺皮质激素细胞肿瘤的细胞组成和转录组。一系列的成绩单相关的激素加工肽酶和基因参与的结构组织的分泌囊泡减少沉默相比，积极的促肾上腺皮质激素肿瘤。与它们的侵袭行为最相关的是，沉默型促肾上腺皮质激素细胞肿瘤表现出上皮-间充质转化（EMT）的几个特征，其中间充质基因的表达增加沿着调节激素生物发生和分泌的转录物的丢失。沉默促肾上腺皮质激素细胞肿瘤血管平滑肌细胞和周细胞基质细胞群体也表现出可塑性，在他们的间充质功能。我们的研究结果提供了新的见解，在沉默的促肾上腺皮质激素细胞肿瘤受损的POMC加工和入侵的机制，并表明，一个共同的转录重编程机制，同时损害POMC加工和激活肿瘤侵袭。
Provide insights into the defective POMC processing and invasive behavior in silent pituitary corticotroph tumors. Single cell RNAseq was used to compare the cellular makeup and transcriptome of silent and active corticotroph tumors. A series of transcripts related to hormone processing peptidases and genes involved in the structural organization of secretory vesicles were reduced in silent compared to active corticotroph tumors. Most relevant to their invasive behavior, silent corticotroph tumors exhibited several features of epithelial-to-mesenchymal transition (EMT), with increased expression of mesenchymal genes along with the loss of transcripts which regulate hormonal biogenesis and secretion. Silent corticotroph tumor vascular smooth muscle cell and pericyte stromal cell populations also exhibited plasticity in their mesenchymal features. Our findings provide novel insights into the mechanisms of impaired POMC processing and invasion in silent corticotroph tumors and suggest that a common transcriptional reprogramming mechanism simultaneously impairs POMC processing and activates tumor invasion.