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Axolotl (Ambystoma mexicanum) is a urodele amphibian endowed with remarkable regenerative capacities manifested in scarless wound healing and restoration of amputated limbs, which makes it a powerful experimental model for regenerative biology and medicine. Previous studies have utilized microarrays and RNA-Seq technologies for detecting differentially expressed (DE) genes in different phases of the axolotl limb regeneration. However, sufficient consistency may be lacking due to statistical limitations arising from intra-laboratory analyses. This study aims to bridge such gaps by performing an integrative analysis of publicly available microarray and RNA-Seq data from axolotl limb samples having comparable study designs using the “merging” method. A total of 351 genes were found DE in regenerative samples compared to the control in data of both technologies, showing an adjusted p-value < 0.01 and log fold change magnitudes >1. Downstream analyses illustrated consistent correlations of the directionality of DE genes within and between data of both technologies, as well as concordance with the literature on regeneration related biological processes. qRT-PCR analysis validated the observed expression level differences of five of the top DE genes. Future studies may benefit from the utilized concept and approach for enhanced statistical power and robust discovery of biomarkers of regeneration.

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Cancer Hallmarks have been indispensable to rationalize the complex phenotypic properties acquired by cancer cells and their surrounding tumor microenvironment (TME) as they progress from normalcy to malignancy. While great insights have been gained from their use to understand bulk tissue transcriptomics, our knowledge remained incomplete, as it was not possible to determine the origin and relative localization of the activity of each Cancer Hallmark within tumor tissues. Thanks to recent advances in spatial transcriptomics, we can now explore the spatial contribution of each compartment within a tumor to each Cancer Hallmark at near single-cell resolution. Here, we used spatial transcriptomics from fifteen different primary tumor samples from seven tissues to quantify the contribution of the main tumor compartments -cancer cells and the TME- to each of thirteen Cancer Hallmarks. Our results revealed a Pan-Cancer architecture: with the activity of some hallmarks consistently coming from the cancer compartment across all cancer types (Cancer-associated hallmarks) and the activity of others consistently coming from the TME (TME-associated hallmarks). Furthermore, we observed that even within each compartment (cancer or TME) there was a consistent internal architecture, as many of these hallmarks exhibited higher activity at the border between compartments. Our study provides the first spatial map of Cancer Hallmark activities in tumors at almost cellular resolution, paving the way for a better understanding of the underpinnings of hallmark acquisition by tumor cell types.

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The axolotl (Ambystoma Mexicanum) salamander, an urodele amphibian, has an exceptional regenerative capacity to fully restore an amputated limb throughout the life-long lasting neoteny. By contrast, when axolotls are experimentally induced to metamorphosis, attenuation of the limb's regenerative competence is noticeable. Here, we sought to discern the proteomic profiles of the early stages of blastema formation of neotenic and metamorphic axolotls after limb amputation by means of LC-MS/MS technology. We quantified a total of 714 proteins having an adjusted p < 0.01 with FC greater or equal to 2 between two conditions. Principal component analysis revealed a conspicuous clustering between neotenic and metamorphic samples at 7 days post-amputation. Different set of proteins was identified as differentially expressed at all of the time points (1, 4, and 7 days post-amputations against day0) for neotenic and metamorphic stages. Although functional enrichment analyses underline the presence of common pathways between regenerative and nonregenerative stages, cell proliferation and its regulation associated pathways, immune system related pathways and muscle tissue and ECM remodeling and degradation pathways were represented at different rate between both stages. To validate the proteomics results and provide evidence for the putative link between immune system activity and regenerative potential, qRT-PCR for selected genes was performed.