Immortalization and characterization of Schwann cell lines derived from NF1-associated cutaneous neurofibromas

Hua Li; Alexander Pemov; Robert Allaway; David F Muir; Lung-Ji Chang; Jineta Banerjee; Alexandra J Scott; Jaime M W Nagy; Jian Liu; Meritxell Carrió; Helena Mazuelas; Anthony Yachnis; Sang Y Lee; Xiaochun Zhang; Yang Lyu; Douglas R Stewart; Angela Hirbe; Jaishri O Blakeley; Eduard Serra; Deeann Wallis; Margaret R Wallace

doi:10.1371/journal.pone.0340183

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Immortalization and characterization of Schwann cell lines derived from NF1-associated cutaneous neurofibromas

Journal article

Open access

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Immortalization and characterization of Schwann cell lines derived from NF1-associated cutaneous neurofibromas

Hua Li, Alexander Pemov, Robert Allaway, David F Muir, Lung-Ji Chang, Jineta Banerjee, Alexandra J Scott, Jaime M W Nagy, Jian Liu, Meritxell Carrió, …

PloS one, Vol.21(1), e0340183

2026

DOI: 10.1371/journal.pone.0340183

PMCID: PMC12822933

PMID: 41564118

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Abstract

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition in which patients are heterozygous for a disruptive pathogenic variant in the NF1 gene. The most characteristic feature of the condition NF1 is the neurofibroma, a benign, multi-cellular tumor which initiates when a cell of the Schwann cell lineage gains a somatic pathogenic variant of the other NF1 allele. Neurofibromas developing at nerve termini in the skin are termed "cutaneous" neurofibromas (cNFs), while those developing within larger nerves are termed "plexiform." Most patients develop cNFs beginning in late childhood or early adulthood, continuing throughout life at variable rates. Some patients may develop only a few cNFs, while others suffer from thousands. There are no reliably effective physical or pharmaceutical therapies besides surgical removal. Although these are not life-threatening, they are disfiguring and can interfere with normal life functions. To provide a resource for research, we developed short-term cNF Schwann cell cultures from NF1 patients, from which we subsequently established the first semi-immortalized cNF cell lines through transduction with wild-type human telomerase reverse transcriptase (hTERT) and murine cyclin-dependent kinase 4 (mCdk4) genes. Here we present molecular, cellular, and functional characterization of these cell lines, which will be of utility for investigating and developing NF1 cNF therapies.

Animals

Cell Line, Tumor

Cyclin-Dependent Kinase 4 - genetics

Cyclin-Dependent Kinase 4 - metabolism

Humans

Mice

Neurofibroma - genetics

Neurofibroma - metabolism

Neurofibroma - pathology

Neurofibromatosis 1 - genetics

Neurofibromatosis 1 - metabolism

Neurofibromatosis 1 - pathology

Neurofibromin 1 - genetics

Schwann Cells - metabolism

Schwann Cells - pathology

Skin Neoplasms - genetics

Skin Neoplasms - metabolism

Skin Neoplasms - pathology

Telomerase - genetics

Telomerase - metabolism

Details

Title: Subtitle: Immortalization and characterization of Schwann cell lines derived from NF1-associated cutaneous neurofibromas
Creators: Hua Li - University of Florida
Alexander Pemov - National Institutes of Health
Robert Allaway - Sage Bionetworks
David F Muir - University of Florida
Lung-Ji Chang - Shenzhen Genoimmune Medical Institute
Jineta Banerjee - Sage Bionetworks
Alexandra J Scott - Sage Bionetworks
Jaime M W Nagy - University of Iowa
Jian Liu - University of Alabama at Birmingham
Meritxell Carrió - Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
Helena Mazuelas - Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
Anthony Yachnis - University of Florida
Sang Y Lee - Johns Hopkins University School of Medicine
Xiaochun Zhang - Washington University in St. Louis
Yang Lyu - Washington University in St. Louis
Douglas R Stewart - National Institutes of Health
Angela Hirbe - Washington University in St. Louis
Jaishri O Blakeley - Johns Hopkins University School of Medicine
Eduard Serra - Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol
Deeann Wallis - University of Alabama at Birmingham
Margaret R Wallace - University of Florida
Resource Type: Journal article
Publication Details: PloS one, Vol.21(1), e0340183
DOI: 10.1371/journal.pone.0340183
PMID: 41564118
PMCID: PMC12822933
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: PloS
Grant note: Division of Cancer Epidemiology and Genetics, National Cancer Institute: Z01CP010144-18 Gilbert Family FoundationNeurofibromatosis Therapeutic Acceleration Program: 185709
We thank the patients and their healthcare providers who contributed the original tissue samples and clinical data. This publication was supported by a subagreement from the Johns Hopkins University via the Neurofibromatosis Therapeutic Acceleration Program (NTAP) with funds to Dr. Wallace provided by a Grant Agreement from the Bloomberg Family Foundation. This publication's contents are solely the responsibility of the authors and do not necessarily represent the official views of the Bloomberg Family Foundation or the Johns Hopkins University. Other support for this work includes: Gilbert Family Foundation's Gene Therapy Initiative (Dr. Wallis); the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, and National Institutes of Health (Drs. Stewart and Pemov); NTAP cNF initiative project (Dr. Serra); NTAP Data and Knowledge Portal for NF1 (Dr. Allaway and Dr. Banerjee).
Language: English
Date published: 2026
Academic Unit: Stead Family Department of Pediatrics; Medical Genetics and Genomics
Record Identifier: 9985130237302771

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