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Series GSE232766 Query DataSets for GSE232766
Status Public on Oct 04, 2023
Title Integration of single-nuclei RNA-sequencing and spatial transcriptomics defines the complex microenvironment of NF1-associated plexiform neurofibromas
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Plexiform neurofibroma (PN) are a leading cause of morbidity in Neurofibromatosis Type 1 (NF1), often disfiguring or threatening vital structures. During formation of PN, a complex tumor microenvironment (TME) develops, with recruitment of neoplastic and non-neoplastic cell types being critical for growth and progression. Due to the cohesive cellularity of PN, single-cell RNA-sequencing is difficult and may result in a loss of detection of critical cellular subpopulations, therefor single-nuclei RNA-sequencing (snRNA-seq) was applied retrospectively to 8 frozen PN, a large enough sample cohort required to adequately describe the disease TME. Additionally, 4 frozen PN samples were OCT embedded and spatial transcriptomics (ST) was run, adding morphological context to the transcriptomic data generated. Our snRNA-seq analysis definitively charted the heterogeneous cellular subpopulations in the PN TME, with the predominant fraction being fibroblast-like cells. PN have a remarkable amount of inter-sample homogeneity regarding cellular subpopulation proportions despite being resected from a variety of anatomical locations. ST analysis identified distinct cellular subpopulations which were annotated using snRNA-seq data that correlated with histological features. Schwann cell/fibroblast interactions were further characterized by receptor/ligand interaction analysis (CellChat) that was applied to snRNA-seq data. A high probability of Neurexin 1/Neuroligin 1 (NRXN1/NRGLN1) receptor-ligand crosstalk was predicted between non-myelinated Schwann cells (NM_SC) and fibroblast subpopulations, respectively. We observed aberrant expression of NRXN1 and NRGLN1 in our snRNA-seq data versus normal mouse sciatic nerve. This pathway has never been described in PN but has been observed in other NF1-associated tumors and may indicate a clear and direct communication pathway between putative NM_SC cells of origin and surrounding fibroblasts, potentially driving disease progression. SnRNA-seq integrated with spatial transcriptomics advances our understanding of the complex cellular heterogeneity of PN. These data identify potential novel communication pathways that may drive disease progression, a finding that could provide translational therapy options for patients with these devastating tumors of childhood and early adulthood.
Overall design single cell RNA-seq and spatial transcriptomic profiling of plexiform neurofibroma

Please note that the records have been updated with an additional sample record on Mar 20, 2024.
Contributor(s) Amani V, Riemondy K, Donson A, Willard N
Citation(s) 37770931
Submission date May 17, 2023
Last update date Mar 21, 2024
Contact name Vladimir Amani
Phone 3037242399
Organization name University of Colorado Anschutz Medical Campus
Street address 12800 East 19th Avenue, Building: RC-1 North; Room: P184402A
City Aurora
State/province CO
ZIP/Postal code 80045
Country USA
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (12)
GSM7373494 NF02
GSM7373495 NF09
GSM7373496 NF12
BioProject PRJNA973725

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE232766_RAW.tar 210.8 Mb (http)(custom) TAR (of JPG)
GSE232766_single_nuclei_barcodes.tsv.gz 125.7 Kb (ftp)(http) TSV
GSE232766_single_nuclei_features.tsv.gz 205.3 Kb (ftp)(http) TSV
GSE232766_single_nuclei_matrix.mtx.gz 164.9 Mb (ftp)(http) MTX
GSE232766_single_nuclei_metadata.csv.gz 170.9 Kb (ftp)(http) CSV
GSE232766_spacerangerout.tar.gz 148.9 Mb (ftp)(http) TAR
GSE232766_spatial_barcodes.tsv.gz 43.4 Kb (ftp)(http) TSV
GSE232766_spatial_features.tsv.gz 234.1 Kb (ftp)(http) TSV
GSE232766_spatial_matrix.mtx.gz 32.4 Mb (ftp)(http) MTX
GSE232766_spatial_metadata.csv.gz 222.7 Kb (ftp)(http) CSV
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Processed data are available on Series record

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