TY - JOUR
T1 - Human cutaneous neurofibroma matrisome revealed by single-cell RNA sequencing
AU - Brosseau, Jean Philippe
AU - Sathe, Adwait A.
AU - Wang, Yong
AU - Nguyen, Toan
AU - Glass, Donald A.
AU - Xing, Chao
AU - Le, Lu Q.
N1 - Funding Information:
We thank the members of the Le laboratory for helpful discussion and Renee McKay for critical review of the manuscript. JPB is a FRSQ J1 research scholar, a former Young Investigator Awardee from the Children’s Tumor Foundation and a recipient of the Early Investigator Research Award from the US Department of Defense. LQL held a Career Award for Medical Scientists from the Burroughs Wellcome Fund and the Thomas L. Shields, M.D. Professorship in Dermatology. This work was supported by funding from the National Cancer Institute of the National Institutes of Health (Grant Numbers R01 CA166593 and U54 CA196519) and the US Department of Defense (Grant Number W81XWH1910238).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1186/s40478-020-01103-4
DO - 10.1186/s40478-020-01103-4
M3 - Article
C2 - 33413690
AN - SCOPUS:85098868136
SN - 2051-5960
VL - 9
JO - Acta Neuropathologica Communications
JF - Acta Neuropathologica Communications
IS - 1
M1 - 11
ER -