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Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression

ABSTRACT: Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression

PROVIDER: PRJNA697979 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13582776.fastq.gz	Fastqsanger.gz
	SRR13582777.fastq.gz	Fastqsanger.gz
	SRR13582778.fastq.gz	Fastqsanger.gz
	SRR13582779.fastq.gz	Fastqsanger.gz

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Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression

Project description:NF1-associated malignant peripheral nerve sheath tumors (MPNST) are the major cause of mortality in neurofibromatosis. MPNST arise from benign peripheral nerve plexiform neurofibromas (PN) which originate in the embryonic neural crest cell lineage. Using reporter transgenes that label early neural crest lineage cells in multiple NF1 MPNST mouse models, we discovered and characterized a rare MPNST cell population with stem cell-like properties that is essential for tumor initiation and relapse. Following isolation of these cells we derive a cancer stem cell specific gene expression signature that includes consensus embryonic neural crest genes and we also identify Nestin as a novel marker for the MPNST cell of origin. Finally, application of the mouse cancer stem cell signature to single cell sequencing data from a rare NF1-associated MPNST precursors called atypical neurofibromatosis neoplasms of uncertain biologic potential (ANNUBP), identifies preformed unsupervised gene expression cell clusters. Enrichment of the cancer stem cell signature in cognate human tumors supports the generality and relevance of cancer stem cells to therapy development.

2021-04-07 | GSE165826 | GEO

Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression.

Project description:NF1-associated malignant peripheral nerve sheath tumors (MPNSTs) are the major cause of mortality in neurofibromatosis. MPNSTs arise from benign peripheral nerve plexiform neurofibromas that originate in the embryonic neural crest cell lineage. Using reporter transgenes that label early neural crest lineage cells in multiple NF1 MPNST mouse models, we discover and characterize a rare MPNST cell population with stem-cell-like properties, including quiescence, that is essential for tumor initiation and relapse. Following isolation of these cells, we derive a cancer-stem-cell-specific gene expression signature that includes consensus embryonic neural crest genes and identify Nestin as a marker for the MPNST cell of origin. Combined targeting of cancer stem cells along with antimitotic chemotherapy yields effective tumor inhibition and prolongs survival. Enrichment of the cancer stem cell signature in cognate human tumors supports the generality and relevance of cancer stem cells to MPNST therapy development.

| S-EPMC8349880 | biostudies-literature

Effect of RRM2 knockdown on gene expression of NF1-associated MPNST cells

Project description:To investigate the role of RRM2 in the progression of NF1-associated MPNST, we established S462TY cell in which target gene has been knocked down by shRNA. We then performed gene expression profiling analysis using data obtained from RNA-seq of control and knockdown of target gene group

2022-09-26 | GSE213988 | GEO

RNA Sequencing of murine MPNST Tumors

Project description:We utilized three murine MPNST cell lines. 67C-4 and #5NPCIS cell lines are derived from spontaneously arising tumors in mice mutated for NF1 and p53 (so-called NP-cis mice; PMID: 12154062). SN4-4 cells originated from MPNST tumors induced by injecting adenovirus containing Cas9 and guide RNA for Nf1 and p53 into the sciatic nerves, resulting in NF1/p53-null MPNST (PMID: 32456131). We implanted 5 x 10^6 murine MPNST cells, subcutaneously, into the flanks of 6-8 weeks old gender-matched C57BL/6 mice (for 67C-4 and #5NPCIS) and BALB/c mice (for SN4-4 mice) to generate MPNST tumors. All mice were procured from Envigo. Upon reaching a size of 300-500 mm3, the mice were euthanized to harvest the tumors, which were subsequently flash frozen using liquid nitrogen and processed for RNA sequencing.

2024-06-19 | GSE244829 | GEO

Effect of p53 knockout on gene expression during capmatinib treatment of NF1-MET murine MPNST cells

Project description:To investigate the function of p53 in regulating response to MET inhibition in MPNST cells we established NF1-MET;sgP53 cells in which Trp53 was knocked out using CRISPR-Cas9. As a control, the parental NF1-MET was transduced with CRISPR-Cas9 in the absence of sgRNA. We then performed gene expression profiling analysis using data obtained from RNA-seq of the 2 different cells treated with either capmatinib or vehicle in duplicate.

2024-03-14 | GSE225747 | GEO

Cdkn2a loss in a model of neurofibroma demonstrates stepwise tumor progression to atypical neurofibroma and MPNST

Project description:Plexiform neurofibromas (PN) are benign nerve sheath Schwann cell tumors, common in patients with neurofibromatosis type 1 (NF1), that are characterized by biallelic mutations in the NF1 tumor suppressor gene. Atypical neurofibromas (ANF) show additional frequent loss of CDKN2A/Ink4a/Arf and may be precursor lesions of aggressive malignant peripheral nerve sheath tumors (MPNST). We combined loss of Nf1 in developing

2020-12-23 | GSE148249 | GEO

Array-CGH of malignant peripheral nerve sheath tumors (MPNST)

Project description:Comparison of copy number changes in MPNST samples against benign neurofibromas in NF1 patients 24 MPNSTs and 3 NF samples were hybridised to the human 32K BAC tiling path array

2010-05-18 | E-GEOD-16041 | biostudies-arrayexpress

Array-CGH of malignant peripheral nerve sheath tumors (MPNST)

Project description:Comparison of copy number changes in MPNST samples against benign neurofibromas in NF1 patients

2009-05-20 | GSE16041 | GEO

Spatial gene expression profiling unveils immuno-oncogenic programs of NF1-associated peripheral nerve sheath tumor progression

Project description:Plexiform neurofibromas (PNF) are benign peripheral nerve sheath tumors (PNST) that arise in persons with neurofibromatosis type 1 (NF1). Despite similar histological appearance, these neoplasms proceed along diverse evolutionary trajectories, with a subset progressing to a devastating form of sarcoma called malignant peripheral nerve sheath tumor (MPNST), the leading cause of premature death in individuals with NF1. Malignant transformation of PNF often occurs through the development of atypical neurofibroma (ANF) precursor lesions characterized by distinct histopathological features and CDKN2A copy number loss. While genomic studies have improved our understanding of key driver events promoting tumor progression, the transcriptional alterations that precede malignant transformation remain poorly understood. Here we resolve gene expression profiles in PNSTs across the neurofibroma-to-MPNST continuum in NF1 patients and genetically engineered mouse models, providing insight into nascent molecular features associated with neurofibroma evolution and transformation. These findings highlight the need for molecular diagnostic tools that augment conventional histopathological criteria to identify neurofibromas at high risk of undergoing malignant transformation, facilitating risk-adapted care.

2023-12-14 | GSE239561 | GEO

Effect of RRM2 knockdown on gene expression of NF1-associated MPNST cells

Project description:Effect of RRM2 knockdown on gene expression of NF1-associated MPNST cells

| PRJNA883419 | ENA