{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T11:05:45Z","timestamp":1772190345746,"version":"3.50.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"Supplement_1","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas arising from Schwann cells and characterized by marked cellular and molecular heterogeneity. Although bulk multi-omic studies have provided valuable insights into MPNST biology, recent advances in single-cell profiling have deepened our understanding of the tumor microenvironment and molecular mechanisms underlying malignant transformation. Single cell analyses have revealed distinct Schwann cell-like, malignant neural crest-like, immune, and stromal cellular subpopulations within MPNSTs and their precursor lesions. Comparative profiling of MPNSTs, neurofibromas, and atypical neurofibromatous neoplasms of uncertain biologic potential, suggest that MPNST progression involves Schwann cell dedifferentiation into a more primitive, stem-like state. In this review, we summarize key discoveries from single-cell characterization studies, and discuss how these findings illuminate MPNST tumorigenesis, cellular plasticity, and potential therapeutic vulnerabilities.<\/jats:p>","DOI":"10.1093\/noajnl\/vdaf243","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T13:07:03Z","timestamp":1764248823000},"page":"i43-i50","source":"Crossref","is-referenced-by-count":0,"title":["Single-cell transcriptomic profiling of malignant peripheral nerve sheath tumors"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6685-1970","authenticated-orcid":false,"given":"Chloe","family":"Gui","sequence":"first","affiliation":[{"name":"MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto , Toronto (C.G., S.B., M.L., S.S.)"},{"name":"Division of Neurosurgery, Department of Surgery, University of Toronto , Toronto (C.G., S.S.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Severa","family":"Bunda","sequence":"additional","affiliation":[{"name":"MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto , Toronto (C.G., S.B., M.L., S.S.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mira","family":"Li","sequence":"additional","affiliation":[{"name":"MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto , Toronto (C.G., S.B., M.L., S.S.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mayo Clinic , Rochester (O.S., G.Z.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gelareh","family":"Zadeh","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mayo Clinic , Rochester (O.S., G.Z.)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suganth","family":"Suppiah","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery, University of Toronto , Toronto (C.G., S.S.)"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"2026022705013673700_vdaf243-B1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/2045-3329-2-17","article-title":"Malignant peripheral nerve sheath tumours in inherited disease","volume":"2","author":"Gareth","year":"2012","journal-title":"Clin Sarcoma Res"},{"issue":"5","key":"2026022705013673700_vdaf243-B2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1136\/jmg.39.5.311","article-title":"Malignant peripheral nerve sheath tumours in neurofibromatosis 1","volume":"39","author":"Evans","year":"2002","journal-title":"J Med Genet"},{"key":"2026022705013673700_vdaf243-B3","doi-asserted-by":"publisher","first-page":"142","DOI":"10.3171\/2012.9.JNS101610","article-title":"Role of resection of malignant peripheral nerve sheath tumors in patients with neurofibromatosis type 1","volume":"118","author":"Dunn","year":"2013","journal-title":"J Neurosurg"},{"key":"2026022705013673700_vdaf243-B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/J.HUMPATH.2017.05.010","article-title":"Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview","volume":"67","author":"Miettinen","year":"2017","journal-title":"Hum Pathol"},{"key":"2026022705013673700_vdaf243-B5","doi-asserted-by":"publisher","first-page":"2696","DOI":"10.1038\/s41467-023-38432-6","article-title":"Multiplatform molecular profiling uncovers two subgroups of malignant peripheral nerve sheath tumors with distinct therapeutic vulnerabilities","volume":"14","author":"Suppiah","year":"2023","journal-title":"Nat Commun"},{"key":"2026022705013673700_vdaf243-B6","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1038\/NG.3095","article-title":"PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors","volume":"46","author":"Lee","year":"2014","journal-title":"Nat Genet"},{"key":"2026022705013673700_vdaf243-B7","doi-asserted-by":"publisher","first-page":"e157502","DOI":"10.1172\/jci.insight.157502","article-title":"PRC2 loss drives MPNST metastasis and matrix remodeling","volume":"7","author":"Brockman","year":"2022","journal-title":"JCI Insight"},{"key":"2026022705013673700_vdaf243-B8","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1038\/ng.3095","article-title":"PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors","volume":"46","author":"Lee","year":"2014","journal-title":"Nat Genet"},{"key":"2026022705013673700_vdaf243-B9","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/NATURE13561","article-title":"PRC2 loss amplifies ras-driven transcription and confers sensitivity to BRD4-based therapies","volume":"514","author":"De Raedt","year":"2014","journal-title":"Nature"},{"key":"2026022705013673700_vdaf243-B10","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1002\/HUMU.23552","article-title":"Analysis of intratumor heterogeneity in neurofibromatosis type 1 plexiform neurofibromas and neurofibromas with atypical features: correlating histological and genomic findings","volume":"39","author":"Carri\u00f3","year":"2018","journal-title":"Hum Mutat"},{"key":"2026022705013673700_vdaf243-B11","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1038\/NG.3095","article-title":"PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors","volume":"46","author":"Lee","year":"2014","journal-title":"Nat Genet"},{"key":"2026022705013673700_vdaf243-B12","doi-asserted-by":"publisher","first-page":"a026575","DOI":"10.1101\/CSHPERSPECT.A026575","article-title":"Role of the polycomb repressive complex 2 (PRC2) in transcriptional regulation and cancer","volume":"6","author":"Laugesen","year":"2016","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2026022705013673700_vdaf243-B13","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1007\/s00401-021-02341-z","article-title":"Enhancer reprogramming in PRC2-deficient malignant peripheral nerve sheath tumors induces a targetable de-differentiated state","volume":"142","author":"Kochat","year":"2021","journal-title":"Acta Neuropathol"},{"key":"2026022705013673700_vdaf243-B14","doi-asserted-by":"publisher","first-page":"499","DOI":"10.3390\/genes11050499","article-title":"Unmasking intra-tumoral heterogeneity and clonal evolution in NF1-MPNST","volume":"11","author":"Moon","year":"2020","journal-title":"Genes (Basel)"},{"key":"2026022705013673700_vdaf243-B15","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41467-024-44755-9","article-title":"Functional interactions between neurofibromatosis tumor suppressors underlie schwann cell tumor de-differentiation and treatment resistance","volume":"15","author":"Vasudevan","year":"2024","journal-title":"Nat Commun"},{"key":"2026022705013673700_vdaf243-B16","doi-asserted-by":"publisher","first-page":"eabo5442","DOI":"10.1126\/sciadv.abo5442","article-title":"Single-cell multiomics identifies clinically relevant mesenchymal stem-like cells and key regulators for MPNST malignancy","volume":"8","author":"Wu","year":"2022","journal-title":"Sci Adv"},{"key":"2026022705013673700_vdaf243-B17","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1016\/J.STEM.2021.04.029\/ATTACHMENT\/9E7FE858-8E4F-4DCF-86D8-94A423CD253F\/MMC8.PDF","article-title":"Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression","volume":"28","author":"Sun","year":"2021","journal-title":"Cell Stem Cell"},{"key":"2026022705013673700_vdaf243-B18","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/s40478-023-01639-1","article-title":"Integration of single-nuclei RNA-sequencing, spatial transcriptomics and histochemistry defines the complex microenvironment of NF1-associated plexiform neurofibromas","volume":"11","author":"Amani","year":"2023","journal-title":"Acta Neuropathol Commun"},{"key":"2026022705013673700_vdaf243-B19","doi-asserted-by":"publisher","first-page":"eabo5442","DOI":"10.1126\/sciadv.abo5442","article-title":"Single-cell multiomics identifies clinically relevant mesenchymal stem-like cells and key regulators for MPNST malignancy","volume":"8","author":"Wu","year":"2022","journal-title":"Sci Adv"},{"key":"2026022705013673700_vdaf243-B20","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1158\/2159-8290.CD-20-1808","article-title":"Therapeutic targeting of the tumor microenvironment","volume":"11","author":"Bejarano","year":"2021","journal-title":"Cancer Discov"},{"key":"2026022705013673700_vdaf243-B21","doi-asserted-by":"publisher","first-page":"e146351","DOI":"10.1172\/jci","author":"Dehner","year":"2021"},{"key":"2026022705013673700_vdaf243-B22","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/s41596-024-01045-4","article-title":"CellChat for systematic analysis of cell\u2013cell communication from single-cell transcriptomics","volume":"20","author":"Jin","year":"2025","journal-title":"Nat Protoc"},{"key":"2026022705013673700_vdaf243-B23","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1158\/1078-0432.CCR-23-2548","article-title":"Spatial Gene-Expression profiling unveils immuno-oncogenic programs of NF1-Associated peripheral nerve sheath tumor progression","volume":"30","author":"Mitchell","year":"2024","journal-title":"Clin Cancer Res"},{"key":"2026022705013673700_vdaf243-B24","doi-asserted-by":"publisher","first-page":"104829","DOI":"10.1016\/j.ebiom.2023.104829","article-title":"Transcriptomic subtyping of malignant peripheral nerve sheath tumours highlights immune signatures, genomic profiles, patient survival and therapeutic targets","volume":"97","author":"H\u00f8land","year":"2023","journal-title":"EBioMedicine"},{"key":"2026022705013673700_vdaf243-B25","doi-asserted-by":"publisher","first-page":"e2400083","DOI":"10.1200\/oa-24-00083","article-title":"Phase II study of pexidartinib plus sirolimus in unresectable malignant peripheral nerve sheath tumors identifies M2 macrophage activation","volume":"2","author":"Manji","year":"2025","journal-title":"JCO Oncol Adv"},{"key":"2026022705013673700_vdaf243-B26","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.ccr.2008.01.003","article-title":"The loss of Nf1 transiently promotes Self-Renewal but not tumorigenesis by neural crest stem cells","volume":"13","author":"Joseph","year":"2008","journal-title":"Cancer Cell"},{"key":"2026022705013673700_vdaf243-B27","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/J.CCELL.2014.09.009\/ATTACHMENT\/87DEE081-8142-4641-8161-B3BA4AC550D6\/MMC2.PDF","article-title":"Cells of origin in the embryonic nerve roots for NF1-Associated plexiform neurofibroma","volume":"26","author":"Chen","year":"2014","journal-title":"Cancer Cell"},{"key":"2026022705013673700_vdaf243-B28","doi-asserted-by":"publisher","first-page":"291","DOI":"10.4149\/NEO_2010_04_291","article-title":"Nestin expression in human tumors and tumor cell lines","volume":"57","author":"Krupkova","year":"2010","journal-title":"Neoplasma"},{"key":"2026022705013673700_vdaf243-B29","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1093\/neuonc\/noaf016","article-title":"Spatially resolved transcriptomics of benign and malignant peripheral nerve sheath tumors","volume":"27","author":"Bremer","year":"2025","journal-title":"Neuro Oncol"},{"key":"2026022705013673700_vdaf243-B30","doi-asserted-by":"publisher","first-page":"111363","DOI":"10.1016\/j.celrep.2022.111363","article-title":"Single-cell sequencing reveals activation of core transcription factors in PRC2-deficient malignant peripheral nerve sheath tumor","volume":"40","author":"Zhang","year":"2022","journal-title":"Cell Rep"},{"key":"2026022705013673700_vdaf243-B31","doi-asserted-by":"publisher","first-page":"e108780","DOI":"10.15252\/embj.2021108780","article-title":"Schwann cell precursors represent a neural crest-like state with biased multipotency","volume":"41","author":"Kastriti","year":"2022","journal-title":"Embo J"},{"key":"2026022705013673700_vdaf243-B32","doi-asserted-by":"publisher","first-page":"e153437","DOI":"10.1172\/JCI153437","article-title":"Tumor-intrinsic PRC2 inactivation drives a context-dependent immune-desert microenvironment and is sensitized by immunogenic viruses","volume":"132","author":"Yan","year":"2022","journal-title":"J Clin Invest"},{"key":"2026022705013673700_vdaf243-B33","doi-asserted-by":"publisher","first-page":"4142","DOI":"10.1158\/1078-0432.CCR-20-5032\/672206\/AM\/FDA-APPROVAL-SUMMARY-SELUMETINIB-FOR-PLEXIFORM","article-title":"FDA approval summary: selumetinib for plexiform neurofibroma","volume":"27","author":"Casey","year":"2021","journal-title":"Clin Cancer Res"},{"key":"2026022705013673700_vdaf243-B34","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1056\/nejmoa1912735","article-title":"Selumetinib in children with inoperable plexiform neurofibromas","volume":"382","author":"Gross","year":"2020","journal-title":"N Engl J Med"},{"key":"2026022705013673700_vdaf243-B35","doi-asserted-by":"publisher","first-page":"2550","DOI":"10.1056\/nejmoa1605943","article-title":"Activity of selumetinib in neurofibromatosis type 1\u2013related plexiform neurofibromas","volume":"375","author":"Dombi","year":"2016","journal-title":"N Engl J Med"},{"key":"2026022705013673700_vdaf243-B36","doi-asserted-by":"publisher","first-page":"5459","DOI":"10.1158\/1078-0432.CCR-24-1454","article-title":"Multidimensional immunotyping of human NF1-Associated peripheral nerve sheath tumors uncovers Tumor-Associated macrophages as key drivers of immune evasion in the tumor microenvironment","volume":"30","author":"Zhang","year":"2024","journal-title":"Clin Cancer Res"},{"key":"2026022705013673700_vdaf243-B37","doi-asserted-by":"publisher","first-page":"e58591","DOI":"10.7554\/ELIFE.58591","article-title":"Transcriptional profiling of mouse peripheral nerves to the single-cell level to build a sciatic nerve atlas (Snat)","volume":"10","author":"Gerber","year":"2021","journal-title":"Elife"},{"key":"2026022705013673700_vdaf243-B38","doi-asserted-by":"publisher","first-page":"2749","DOI":"10.1038\/nprot.201.012","author":"Shen","year":"2019"},{"key":"2026022705013673700_vdaf243-B39","doi-asserted-by":"publisher","first-page":"2737","DOI":"10.1038\/s41591-023-02605-z","article-title":"Liquid biopsy epigenomic profiling for cancer subtyping","volume":"29","author":"Baca","year":"2023","journal-title":"Nat Med"}],"container-title":["Neuro-Oncology Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/noa\/article-pdf\/8\/Supplement_1\/i43\/67138488\/vdaf243.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/noa\/article-pdf\/8\/Supplement_1\/i43\/67138488\/vdaf243.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:01:50Z","timestamp":1772186510000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/noa\/article\/8\/Supplement_1\/i43\/8499782"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":39,"journal-issue":{"issue":"Supplement_1","published-print":{"date-parts":[[2026,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/noajnl\/vdaf243","relation":{},"ISSN":["2632-2498"],"issn-type":[{"value":"2632-2498","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,3]]},"published":{"date-parts":[[2026,2,18]]}}}