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Series GSE244119 Query DataSets for GSE244119
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 and RPMA GBC-derived allograft tumors, CellTagged]
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 normal globose basal cells (GBCs) via immunomagnetic selection for KIT from the pooled olfactory epithelium of n=3-4 Rb1 fl/fl; Trp53 fl/fl; Myc T58A (RPM) or Rb1 fl/fl; Trp53 fl/fl; Myc T58A; Ascl1 fl/fl (RPMA) mice, not exposed to Cre, 10 days following methimazole lesioning. RPM and RPMA GBCs were transformed by treatment with Cre and transduced with a lentiviral barcode-based lineage-tracing technology termed CellTag V1 (established by Samantha Morris's lab, Kong et al., Nature Protocols, 2020). Transformed, CellTagged GBC's were implanted with Matrigel into the flanks of Scid/Beige mice. Upon outgrowth of the GBC-organoid-derived allografts, tumor cells were collected and processed for single-cell RNA sequencing. Allograft tumors were processed into single cell suspensions, and subject to 10X Genomics single-cell gene expression library construction (Dual-Index 3' GEX) followed by 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 (2)
GSM7807594 RPMA GBC Allograft rep1
GSM8149580 RPM GBC Allograft rep1
This SubSeries is part of SuperSeries:
GSE244123 Olfactory neuroblastoma mimics molecular subtypes and lineage trajectories of small cell lung cancer
Relations
BioProject PRJNA1021257

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Supplementary file Size Download File type/resource
GSE244119_RAW.tar 335.0 Mb (http)(custom) TAR (of TAR)
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Raw data are available in SRA

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