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Series GSE244122 Query DataSets for GSE244122
Status Public on May 15, 2024
Title Olfactory neuroblastoma mimics molecular subtypes and lineage trajectories of small cell lung cancer [Single cell RNA seq on RPM-GFP and RPMA ONB tumors]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The olfactory epithelium relies on active neuron regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare, aggressive tumor of unclear origins. Here, we establish a new, highly-penetrant, genetically-engineered mouse model of ONB with alterations in Rb1/Trp53/Myc that exhibit a NEUROD1+ immature neuronal state. ASCL1 loss leads to emergence of non-neuronal histopathologies, including a POU2F3+ microvillar-like state. We find ONB tumor heterogeneity to recapitulate developmental states of multipotent globose basal cells (GBCs), which our data demonstrate is a cell of origin for ONB. Similar to small cell lung cancer (SCLC), mouse and human ONB exhibit: mutually exclusive ASCL1, NEUROD1, and POU2F3- like states, an immune-cold tumor microenvironment, intratumoral subtype heterogeneity comprising neuronal and non-neuronal lineages, and subtype plasticity—as evidenced by barcode-based lineage tracing and single-cell transcriptomics. Collectively, our findings highlight conserved developmental trajectories between ONB and SCLC subtypes with significant implications for ONB classification and treatment.
 
Overall design We harvested olfactory neuroblastoma tumor cells from n=1 homozygous Rb1 fl/fl; Trp53 fl/fl; H11b-LSL-MycT58A-Ires-Luc (RPM)-Rosa26-LSL-Cas9-Ires-Gfp (RPM-GFP) mouse in which tumor cells are GFP+, and n=3 homozygous Rb1 fl/fl; Trp53 fl/fl; H11b-LSL-MycT58A-Ires-Luc; Ascl1 fl/fl (RPMA) to perform single cell RNA-sequencing (scRNA-seq). Tumors were micro-dissected from the olfactory cavity of each mouse, processed into single cell suspensions, and subject to 10X Genomics single-cell gene expression library construction (Dual-Index 3' GEX) and downstream Illumina-based sequencing.
 
Contributor(s) Ireland A, Oliver T
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Submission date Sep 26, 2023
Last update date May 15, 2024
Contact name Trudy Oliver
E-mail(s) tgo@duke.edu, trudy.oliver@duke.edu
Phone 6174607487
Organization name Duke University
Department Pharmacology & Cancer Biology
Lab theoliverlab
Street address Duke University, Box 3813, LSRC Room C138B, 308 Research Drive
City Durham
State/province NC
ZIP/Postal code 27708
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM7807645 RPM ONB tumor rep1
GSM7807646 RPMA ONB tumor rep1
GSM7807647 RPMA ONB tumor rep2
This SubSeries is part of SuperSeries:
GSE244123 Olfactory neuroblastoma mimics molecular subtypes and lineage trajectories of small cell lung cancer
Relations
BioProject PRJNA1021258

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Supplementary file Size Download File type/resource
GSE244122_RAW.tar 223.0 Mb (http)(custom) TAR (of H5, TAR)
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Raw data are available in SRA

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