单细胞转录揭示成纤维细胞异质性和神经细胞在纤维瘤病中的意义。

IF 4.3 2区 医学 Q1 ONCOLOGY
Cancer Science Pub Date : 2025-07-24 DOI:10.1111/cas.70160
Junfeng Wang, Cheng Zhou, Peng Huang, Haodong Li, Ping Xu, Yiming Zheng, Dahui Wang, Bo Ning
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引用次数: 0

摘要

硬纤维瘤病(Desmoid纤维瘤病,DF)是一种复发率高的难治性肿瘤,可导致严重的器官畸形、发病率和死亡率。DF的细胞特性仍然难以捉摸。在这里,我们进行了单细胞RNA测序(scRNA-seq)来揭示DF的细胞景观。为了揭示DF的独特特征,我们将DF与公开数据(GSE163973)中的瘢痕疙瘩成纤维细胞(KF)和正常成纤维细胞(NF)的转录谱进行了比较。与KF和NF相比,DF中间充质成纤维细胞明显扩增。间充质成纤维细胞根据分化状态进一步分为两种亚型,其中LAMP5+ SULF1+成纤维细胞可能通过促进肿瘤骨化来解释DF的硬性。ADAM12和CREB3L1分别被鉴定为DF的特异性标记物和转录因子。静止和增殖的COL11A1+神经细胞都通过调节细胞外基质在维持DF纤维化微环境中发挥主导作用。本研究首次揭示了DF中成纤维细胞的异质性。在DF中发现的新的基因标记物和转录因子,以及神经细胞在肿瘤微环境中的意义,可能为未来DF的靶向治疗指明新的方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Single-Cell Transcription Reveals the Fibroblast Heterogeneity and Neural Cells' Significance in Desmoid Fibromatosis

Single-Cell Transcription Reveals the Fibroblast Heterogeneity and Neural Cells' Significance in Desmoid Fibromatosis

Desmoid fibromatosis (DF) is a refractory tumor with a high recurrence rate, resulting in severe organ's deformity, morbidity, and mortality. The cellular characteristics of DF remain elusive. Herein, we performed single-cell RNA sequencing (scRNA-seq) to reveal the cell landscape of DF. To uncover the exclusive characteristics of DF, we compared the transcriptional profile of DF with that of keloid fibroblast (KF) and normal fibroblast (NF) in the public data (GSE163973). When compared with KF and NF, mesenchymal fibroblasts were significantly expanded in DF. The mesenchymal fibroblasts were further divided into two subtypes according to the differentiation states, among which LAMP5+ SULF1+ fibroblasts may account for the hard property of DF by promoting tumor ossification. ADAM12 and CREB3L1 were identified as the specific marker and transcription factor for DF, respectively. Both the quiescent and proliferative COL11A1+ neural cells exerted dominant roles in the maintenance of the profibrotic microenvironment in DF through modulating extracellular matrix. This study revealed the heterogeneity of fibroblasts in DF for the first time. The novel gene markers and transcription factor identified in DF and the significance of neural cells in the tumor microenvironment may point to new directions for the targeted therapy of DF in the future.

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来源期刊
Cancer Science
Cancer Science 医学-肿瘤学
自引率
3.50%
发文量
406
审稿时长
2 months
期刊介绍: Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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