Biology subjects

Lopez-Cascales, M. T.

Publications and source records attributed to Lopez-Cascales, M. T..

4 recordsLinked to original sources

bioRxiv2026

Behavior-coupled single-cell transcriptomics reveals trafficking protein-dependent regulation of tumor cell migration

Aggressive cellular migration underlies cancer invasion and metastatic dissemination, yet the molecular programs defining highly migratory tumor cell states remain poorly characterized. In head and neck squamous cell carcinoma (HNSCC), metastatic progression is associated with poor clinical outcome, motivating method developments that link migratory behavior to underlying mechanisms. Here, we present behavior-coupled single-cell sequencing (BC-seq), a live-cell imaging-guided transcriptomic platform that enables real-time identification, isolation, and profiling of individual cells based on migratory behavior. Applying BC-seq to 10 HPV-negative oral squamous cell carcinoma (OSCC), the most common HNSCC subtype, we distinguished fast-migrating cells (FMCs) from slow-migrating cells (SMCs) and identified transcriptional programs associated with aggressive migration. Mechanistically, BC-seq uncovered cholesterol-regulated signaling pathways and associated trafficking proteins involving SREBP2, STARD4, Cavin1/3, and VEGFR2 that promotes actin cytoskeletal remodeling and cellular motility. Disruption of STARD4-mediated cholesterol trafficking or Cavin1/3-dependent VEGFR2 nuclear translocation significantly impaired cell migration, linking cholesterol metabolism to migratory machinery. We next examined whether molecular programs associated with aggressive migration are reflected in clinical outcomes. A 15-gene expression signature derived from FMCs predicted distant metastasis with 83.6% accuracy in an independent OSCC cohort, outperforming conventional clinicopathological risk stratification. Together, our study establishes BC-seq as an approach for integrating dynamic cellular behavior with single-cell transcriptomics to uncover mechanisms of aggressive migration and clinically relevant molecular signatures.

cancer biology↗

bioRxiv2022

Perinatal correlated retinal activity is required for the wiring of visual axons in non-image forming nuclei

The development of the visual system is an intricate and multi-step process involving the precise connection of retinal ganglion cell (RGC) axon terminals with their corresponding neurons in the visual nuclei of the brain. Upon reaching primary image-forming nuclei (IFN), such as the superior colliculus and the lateral geniculate nucleus, RGC axons undergo extensive arborization that refines over the first few postnatal weeks. The molecular mechanisms driving this activity-dependent remodeling process, which is influenced by spontaneous activity in the developing retina, are still not well understood. In this study, by manipulating the activity of RGCs in mice and analyzing their transcriptomic profiles before eye opening, we have identified gene programs involved in activity-dependent refinement. Furthermore, while RGC axons also target non-image forming nuclei (NIFN), the impact of spontaneous retinal activity on the development of these accessory nuclei, has not yet been elucidated. The analysis of visual terminals from mice with altered retinal activity revealed that spontaneous retinal waves occurring prior to visual experience also play a role in shaping the connectivity of the non-image forming circuit. Overall, these findings contribute to a deeper understanding of the mechanisms governing activity-dependent axon refinement during the establishment of the visual circuit.

neuroscience↗

bioRxiv2019

Zic2 abrogates an alternative Wnt signaling pathway to convert axon attraction into repulsion

Wnt signaling is involved in axon pathfinding during brain wiring but it is unknown how Wnt ligands promote attraction or repulsion. In addition, the participation of the canonical ({beta}catenin-dependent transcription) versus non-canonical ({beta}catenin-independent) Wnt pathways in this process remains controversial. Here we show that Wnt5a is expressed at the optic chiasm midline and promotes axon crossing by triggering an alternative Wnt pathway that depends on polarized accumulation of {beta}catenin at the axon terminal but does not activate the canonical pathway. Remarkably, this alternative pathway is silenced by the transcription factor Zic2 in the small subset of ipsilaterally projecting neurons. Zic2 directly regulates genes related to Wnt and Eph signaling that lead to global accumulation of {beta}catenin but triggers its asymmetric phosphorylation to facilitate the steering of the growth cone. This alternative Wnt pathway found in contralateral axons and its Zic2-mediated abrogation in ipsilateral neurons is likely operating in many other contexts requiring a two-way response to Wnt ligands.

developmental biology↗

bioRxiv2019

Immediate and deferred epigenomic signature of neuronal activation

Activity-driven transcription plays an important role in many brain processes, including those underlying memory and epilepsy. Here, we combine the genetic tagging of neuronal nuclei and ribosomes with various sequencing-based techniques to investigate the transcriptional and chromatin changes occurring at hippocampal excitatory neurons upon synchronous activation during status epilepticus and sparse activation during novel context exploration. The transcriptional burst, which affects both nucleus-resident non-coding RNAs and numerous protein-coding genes involved in neuroplasticity, is associated with a dramatic increase in chromatin accessibility of activity-regulated genes and enhancers, de novo binding of activity-regulated transcription factors, augmented promoter-enhancer interactions, and the formation of gene loops that bring together the TSS and TTS of strongly induced genes to sustain the fast re-loading of RNAPII complexes. Remarkably, some chromatin occupancy changes and interactions remain long after neuronal activation and may underlie the changes in neuronal responsiveness and circuit connectivity observed in these neuroplasticity paradigms.

neuroscience↗