Abstract
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.
Highlights
Neurofibromatosis type I (NF1) is a neurocutaneous genetic disorder with a frequency of 1 in 3000 births
Our analyses revealed the type of extracellular matrix (ECM) secreted by each cell type, provided a complete profiling of cNF collagen, and identified specific cNF fibroblast markers that will provide a molecular platform to further explore the biology of cutaneous neurofibroma
Single cell analysis of human cutaneous neurofibroma To determine the repertoire of ECM genes and ECMassociated proteins [21] expressed in cNF, we performed scRNA-Seq
Summary
Neurofibromatosis type I (NF1) is a neurocutaneous genetic disorder with a frequency of 1 in 3000 births. This disease is characterized by the development of skin lesions called cutaneous neurofibromas (cNFs) [1]. Neurofibroma develops as the result of biallelic inactivation in the NF1 tumor suppressor gene in the Schwann cell lineage, leading to an increase in Ras signaling. CNF is a benign tumor with zero malignant potential, it is often disfiguring and a great source of anxiety for NF1 patients. Surgical removal is the only treatment available, but it is impractical in patients with hundreds or thousands of tumors covering their bodies. There is an urgent need to develop effective therapies to reduce tumor burden
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