Biology subjects

Bedoya-Reina, O.

Publications and source records attributed to Bedoya-Reina, O..

4 recordsLinked to original sources

bioRxiv2026

Sympathoadrenal Lineage Plasticity Drives Intratumoral Heterogeneity in Paraganglioma, Neuroblastoma and Composite Tumors Following KIF1Bb-NF1 Loss

Neuroblastoma (NB) and paraganglioma (PPGL) arise from the sympathoadrenal lineage, yet their developmental relationship and heterogeneity remain unclear. Single-cell and spatial transcriptomics revealed shared, spatially organized developmental states, including populations characteristic of the other tumor type, chromaffin-like cells in NB and neuroblast-like cells in PPGL and hybrids co-expressing adjacent states. Deconvolution of an independent PPGL cohort associated metastatic disease most strongly with chromaffin hybrid states, alongside connecting progenitor-like, cycling neuroblast, and early chromaffin identities, whereas non-metastatic tumors were enriched for differentiated late chromaffin identities. In mice, combined loss of the candidate 1p36 tumor suppressor KIF1B{beta} and NF1 recapitulates these developmental architectures by prolonging developmental plasticity, reactivating embryonic neurogenic programs, and driving chromaffin-to-neuroblast transitions generating pheochromocytoma, neuroblastoma and composite tumors. Mouse tumors contained discrete spatial domains of developmental and neoplastic states that mirrored those in human PPGL. Together, our findings establish chromaffin-neuroblast plasticity as a mechanism of sympathoadrenal tumor heterogeneity and identify hybrid developmental states as a potential indicator of plasticity associated with metastatic PPGL.

cancer biology↗

bioRxiv2024

Ephrin-A2 and Phosphoantigen-Mediated Selective Killing of Medulloblastoma by γδT Cells Preserves Neuronal and Stem Cell Integrity

Medulloblastoma (MB) is a pediatric brain tumor that develops in the cerebellum, representing one of the most common malignant brain cancers in children. Standard treatment includes surgery, chemotherapy, and radiation, but despite a 5-year survival rate of approximately 70%, these therapies often lead to significant neurological damage in the developing brain. This underscores the urgent need for less toxic, more effective therapeutic alternatives. Recent advancements in cancer immunotherapy, including immune checkpoint inhibitors and CAR-T cell therapy, have revolutionized cancer treatment. One promising avenue is the use of Gamma Delta ({gamma}{delta})T cells, a unique T cell population with potential advantages such as non-alloreactivity, potent tumor cell lysis, and broad antigen recognition. However, their capacity to recognize and target MB cells remains underexplored. To investigate the therapeutic potential of {gamma}{delta}T cells against MB, we analyzed the proportion and status of MB-infiltrated {gamma}{delta}T cells within patient datasets. We next investigated the expression of {gamma}{delta}T cell ligands on MB cells and identified EphA2 receptor and the phosphoantigen/Butyrophilin complex as key ligands, activating V{gamma}9V{delta}1 and V{gamma}9V{delta}2 T cells, respectively, leading to significant MB cell lysis in both monolayer and spheroid models. Importantly, preliminary safety data showed that {gamma}{delta}T cells did not target differentiated neurons or neuroepithelial stem cells derived from induced pluripotent stem cells, underscoring the selectivity and safety of this approach. In conclusion, {gamma}{delta}T cells trigger an efficient and specific killing of MB, and would offer a promising novel therapeutic strategy. Key messagesMedulloblastoma patients often experience significant long-term side effects from current standard treatments. Immunotherapy has emerged as a promising alternative to conventional therapeutic approaches. In our study, we demonstrated that {gamma}{delta}T cells can efficiently and specifically target medulloblastoma cells without causing harm to healthy neuronal tissue. These findings suggest that {gamma}{delta} T cell therapy may provide therapeutic benefits while potentially reducing treatment-related toxicity in medulloblastoma patients.

cancer biology↗

bioRxiv2018

Genomic variants among threatened Acropora corals

Genomic sequence data for non-model organisms are increasingly available requiring the development of efficient and reproducible workflows. Here, we develop the first genomic resources and reproducible workflows for two threatened members of the reef-building coral genus Acropora. We generated genomic sequence data from multiple samples of the Caribbean A. cervicornis (staghorn coral) and A. palmata (elkhorn coral), and predicted millions of nucleotide variants among these two species and the Pacific A. digitifera. A subset of predicted nucleotide variants were verified using restriction length polymorphism assays and proved useful in distinguishing the two Caribbean Acroporids and the hybrid they form (\"A. prolifera\"). Nucleotide variants are freely available from the Galaxy server (usegalaxy.org), and can be analyzed there with computational tools and stored workflows that require only an internet browser. We describe these data and some of the analysis tools, concentrating on fixed differences between A. cervicornis and A. palmata. In particular, we found that fixed amino acid differences between these two species were enriched in proteins associated with development, cellular stress response and the hosts interactions with associated microbes, for instance in the Wnt pathway, ABC transporters and superoxide dismutase. Identified candidate genes may underlie functional differences in the way these threatened species respond to changing environments. Users can expand the presented analyses easily by adding genomic data from additional species as they become available.\n\nArticle SummaryWe provide the first comprehensive genomic resources for two threatened Caribbean reef-building corals in the genus Acropora. We identified genetic differences in key pathways and genes known to be important in the animals response to the environmental disturbances and larval development. We further provide a list of candidate loci for large scale genotyping of these species to gather intra- and interspecies differences between A. cervicornis and A. palmata across their geographic range. All analyses and workflows are made available and can be used as a resource to not only analyze these corals but other non-model organisms.

genomics↗

bioRxiv2018

Cerox1 and microRNA-488-3p noncoding RNAs jointly regulate mitochondrial complex I catalytic activity

To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that Cerox1, an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p. Increased abundance of Cerox1 cooperatively elevates complex I subunit protein abundance and enzymatic activity, decreases reactive oxygen species production, and protects against the complex I inhibitor rotenone. Cerox1 function is conserved across placental mammals: human and mouse orthologues effectively modulate complex I enzymatic activity in mouse and human cells, respectively. Cerox1 is the first lncRNA demonstrated, to our knowledge, to regulate mitochondrial oxidative phosphorylation (OXPHOS) and, with miR-488-3p, represent novel targets for the modulation of complex I activity.

biochemistry↗