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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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			Action	DRS
	SRR26186093.fastq.gz	Fastqsanger.gz
	SRR28357595.fastq.gz	Fastqsanger.gz

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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 neuroblastoma mimics molecular subtypes and lineage trajectories of small cell lung cancer [Single cell RNA seq on RPM-GFP and RPMA ONB tumors]

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Olfactory neuroblastoma mimics molecular subtypes and lineage trajectories of small cell lung cancer [Single cell RNA seq on RPM-GFP and RPMA ONB tumors]

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RPM-1 in vivo affinity-purification proteomics using C. elegans

Project description:To uncover putative RPM-1 protein-protein interactions, we performed a comprehensive series of in vivo affinity-purification proteomics experiments using C. elegans. We utilized integrated transgenes that express RPM-1 fused with a Protein G::Streptavidin binding peptide (GS) affinity tag expressed using the native rpm-1 promoter on an rpm-1 protein null background. Negative control animals expressed an integrated transgene where the GS tag was fused to GFP (GS::GFP) and expressed by the rpm-1 promoter. We also designed a biochemical “trap” using an RPM-1 ligase-dead (RPM-1 LD) site-directed mutant to identify ubiquitination substrates. RPM-1 LD would enrich substrates by trapping them in stalled ubiquitination complexes, as well as preventing proteasome-mediated degradation and elevating substrate levels. RPM-1-binding proteins that are not ubiquitination substrates would bind to both RPM-1 and RPM-1 LD.

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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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