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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]

ABSTRACT: 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]

PROVIDER: PRJNA1021257 | ENA |

REPOSITORIES: ENA

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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]

Project description: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.

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Olfactory stem cell differentiation: horizontal basal cell (HBC) lineage

Project description:The lineage of the horizontal basal cells (HBC) stem cells and other Sox2eGFP-positive cells from the olfactory epithelium were profiled by single-cell RNA-Seq to identify differentiated cells types, intermediate stages, transition states, and to infer the lineage trajectories.

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