Biology subjects

Galindo, J.

Publications and source records attributed to Galindo, J..

5 recordsLinked to original sources

bioRxiv2026

Integrated multi-omic analysis of pediatric metastatic osteosarcoma reveals endothelial cell plasticity and lineage infidelity.

While recent research has increasingly focused on the role of fibroblasts and macrophages in osteosarcoma, the tumor vasculature remains poorly understood, particularly in metastatic disease. To address this gap, we performed single-nuclei multi-ome (RNA+ATAC) sequencing on 24 human metastatic osteosarcoma specimens. We found that endothelial cells adopt a hybrid endothelial-mesenchymal state resembling endothelial-to-mesenchymal transition (EndMT) and that a subset of diploid endothelial cells expresses osteoblastic transcriptional profiles and gene regulatory networks (GRN). Joint copy-number analysis further identified osteosarcoma cells with endothelial transcriptional programs and GRNs, consistent with vascular mimicry. In vitro assays and syngeneic lineage-tracing experiments validated that tumor educated endothelial cells acquire osteoblast-like features. Together, these findings reveal substantial plasticity among endothelial and osteosarcoma cells in human and murine metastatic osteosarcoma, provide new insight into the how the metastatic microenvironment shapes the tumor vasculature, and challenge current models of osteosarcoma biology.

cancer biology↗

bioRxiv2026

Divergence in thermal performance contributes to ecotype maintenance in an intertidal snail: evidence from in-situ transplants

Physiological adaptation across environmental gradients can contribute to ecological speciation by limiting performance outside locally optimal habitats. Intertidal systems provide strong natural thermal gradients, yet the extent to which thermal physiology contributes to divergence across shore height remains poorly resolved. We investigated cardiac thermal performance in two ecotypes of the marine snail Littorina saxatilis occupying different shore heights along the Galician coast (NW Spain): a wave-adapted ecotype on the lower and mid- shore and a crab-resistant ecotype on the mid- and upper shore. Using infrared photoplethysmography, we quantified heart rate responses in both a reciprocal field transplant experiment and laboratory thermal ramping trials. In the field, the Wave ecotype exhibited significantly higher heart rates than Crab ecotype snails under native mid-shore conditions and after 1 day of exposure to upper-shore conditions. However, after 4 days of exposure to the upper shore, Wave ecotype snails showed a marked reduction in cardiac activity, whereas Crab ecotype populations maintained stable heart rates across transplant locations and durations. In laboratory ramping experiments, Crab ecotypes displayed lower baseline cardiac activity and greater thermal insensitivity across the rising phase of the thermal response curve, while the Wave ecotype exhibited higher cardiac performance and an earlier decline in heartrate at high temperatures. Together, these results demonstrate pronounced ecotype divergence in cardiac thermal physiology and suggest that chronic exposure to upper-shore conditions compromises cardiac performance in the Wave ecotype. Such physiological differences likely contribute to vertical zonation and the evolution of barriers to gene flow between these ecotypes.

evolutionary biology↗

bioRxiv2026

Expanding the Promoter Toolbox for Metabolic Engineering in the Lignocellulolytic Thermophile Anaerocellum bescii

Anaerocellum (formerly Caldicellulosiruptor) bescii, an anaerobic, extremely thermophilic (Topt [~]78 {degrees}C) lignocellulolytic bacterium, is a promising chassis for metabolic engineering and next-generation bioprocessing. Yet, a lack of well-characterized genetic parts in A. bescii has hampered metabolic engineering efforts. Here, using a previously developed hyperthermophilic {beta}-galactosidase reporter system, we screened a diverse panel of putative A. bescii promoter sequences, identifying promoters that drove reporter output across a broad range. For a select subset, we mapped their transcriptional start sites (TSSs) and evaluated ribosome binding site (RBS) regions using chimeric promoter constructs. By constructing truncated promoter variants, we defined functional regions within the widely used, high-expression S-layer protein promoter (Pslp) and engineered a compact 99 bp variant that retained substantial reporter activity. Finally, we demonstrated that these new promoters can be used for metabolic engineering by using two newly characterized promoters to express an established thermostable alcohol dehydrogenase from Thermoclostridium stercorarium to drive ethanol production in A. bescii. Together, this work expands and diversifies the A. bescii genetic toolkit, opening doors to future metabolic engineering efforts in this species.

Synthetic Biology↗

bioRxiv2025

Spatial profiling identifies regionally distinct microenvironments and targetable immunosuppressive mechanisms in pediatric osteosarcoma pulmonary metastases.

Osteosarcoma is the most common malignant bone tumor in young patients and remains a significant clinical challenge, particularly in the context of metastatic disease. Despite extensive documentation of genomic alterations in osteosarcoma, studies detailing the immunosuppressive mechanisms within the metastatic osteosarcoma microenvironment are lacking. Our objective was to characterize the spatial transcriptional landscape of metastatic osteosarcoma to reveal these immunosuppressive mechanisms and identify promising therapeutic targets. Here, we performed spatial transcriptional profiling on a cohort of osteosarcoma pulmonary metastases from pediatric patients. We reveal a conserved spatial gene expression pattern resembling a foreign body granuloma, characterized by peripheral inflammatory signaling, fibrocollagenous encapsulation, lymphocyte exclusion, and peritumoral macrophage accumulation. We also show that the intratumoral microenvironment of these lesions lack inflammatory signaling. Additionally, we identified CXCR4 as an actionable immunomodulatory target that bridges both the intratumoral and extratumoral microenvironments and highlights the spatial heterogeneity and complexity of this pathway. Collectively, this study reveals that metastatic osteosarcoma specimens are comprised of multiple regionally distinct immunosuppressive microenvironments.

cancer biology↗

bioRxiv2023

Phenotypic divergence and genomic architecture at two different stages of speciation in a marine snail

Speciation typically occurs over too long a time frame to be observed directly. A way forward is to compare pairs of ecotypes that evolved in parallel in similar contexts but have reached different degrees of reproductive isolation. Such comparisons are possible in the marine snail Littorina saxatilis by contrasting barriers to gene flow between parallel ecotypes in Spain and Sweden. In both countries, divergent ecotypes have evolved to withstand either crab predation or wave action. Here, we explore transects spanning contact zones between the Crab and the Wave ecotypes using low-coverage whole-genome sequencing, morphological and behavioural traits. Despite parallel phenotypic divergence, distinct patterns of differentiation between the ecotypes emerged: a continuous cline in Sweden indicating a weak barrier to gene flow, but two highly genetically and phenotypically divergent, and partly spatially-overlapping clusters in Spain suggesting a much stronger barrier to gene flow. Absence of Spanish early-generation hybrids supported strong isolation, but a low level of gene flow is evident from molecular data. In both countries, highly differentiated loci were located in both shared and private chromosomal inversions but were also present in collinear regions. Despite being considered the same species and showing similar levels of phenotypic divergence, the Spanish ecotypes are much closer to full reproductive isolation than the Swedish ones. Barriers to gene flow of very different strengths between ecotypes within the same species might be explained by dissimilarities in the spatial arrangement of habitats, the selection gradients or the ages of the systems. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/558824v2_ufig2.gif" ALT="Figure 2"> View larger version (38K): org.highwire.dtl.DTLVardef@c72ac4org.highwire.dtl.DTLVardef@1c8cd22org.highwire.dtl.DTLVardef@13ac83org.highwire.dtl.DTLVardef@1a301d6_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract.C_FLOATNO Distinct patterns of divergence between parallel ecotypes in Sweden and Spain. C_FIG

evolutionary biology↗