Department of Dermatology, University of Texas Southwestern Medical Center At Dallas, Dallas, TX, 75390-9069, USA.
Department of Biochemistry and Functional Genomic, Centre de Recherche du Centre Hospitalier de Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, Canada.
Acta Neuropathol Commun. 2021 Jan 7;9(1):11. doi: 10.1186/s40478-020-01103-4.
Neurofibromatosis Type I (NF1) is a neurocutaneous genetic syndrome characterized by a wide spectrum of clinical presentations, including benign peripheral nerve sheath tumor called neurofibroma. These tumors originate from the Schwann cell lineage but other cell types as well as extracellular matrix (ECM) in the neurofibroma microenvironment constitute the majority of the tumor mass. In fact, collagen accounts for up to 50% of the neurofibroma's dry weight. Although the presence of collagens in neurofibroma is indisputable, the exact repertoire of ECM genes and ECM-associated genes (i.e. the matrisome) and their functions are unknown. Here, transcriptome profiling by single-cell RNA sequencing reveals the matrisome of human cutaneous neurofibroma (cNF). We discovered that classic pro-fibrogenic collagen I myofibroblasts are rare in neurofibroma. In contrast, collagen VI, a pro-tumorigenic ECM, is abundant and mainly secreted by neurofibroma fibroblasts. This study also identified potential cell type-specific markers to further elucidate the biology of the cNF microenvironment.
神经纤维瘤病 1 型（NF1）是一种神经皮肤遗传性综合征，其临床特征表现广泛，包括良性周围神经鞘肿瘤，称为神经纤维瘤。这些肿瘤来源于施万细胞谱系，但神经纤维瘤微环境中的其他细胞类型和细胞外基质（ECM）构成了肿瘤的大部分。事实上，胶原占神经纤维瘤干重的 50%。尽管神经纤维瘤中存在胶原是不可争议的，但 ECM 基因和 ECM 相关基因（即基质组）的确切谱及其功能尚不清楚。在这里，单细胞 RNA 测序的转录组分析揭示了人类皮肤神经纤维瘤（cNF）的基质组。我们发现，经典的促纤维化胶原 I 肌成纤维细胞在神经纤维瘤中很少见。相比之下，富含细胞外基质（ECM）的胶原 VI 是一种促肿瘤 ECM，主要由神经纤维瘤成纤维细胞分泌。这项研究还确定了潜在的细胞类型特异性标志物，以进一步阐明 cNF 微环境的生物学特性。
