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| 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
Other
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| 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.
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| 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.
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| 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 |
| E-mail(s) |
vladimir.amani@cuanschutz.edu
|
| 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 |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA973725 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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