Search Results (4)

Prostate cancer (PCa), the most frequent and second most lethal cancer type in men in developed countries, is a highly heterogeneous disease. PCa heterogeneity, therapy resistance, stemness, and lethal progression have been attributed to lineage plasticity, which refers to the ability of neoplastic cells to undergo phenotypic changes under microenvironmental pressures by switching between developmental cell states. What remains to be elucidated is how to identify measurements of lineage plasticity, how to implement them to inform preclinical and clinical research, and, further, how to classify patients and inform therapeutic strategies in the clinic. Recent research has highlighted the crucial role of next-generation sequencing technologies in identifying potential biomarkers associated with lineage plasticity. Here, we review the genomic, transcriptomic, and epigenetic events that have been described in PCa and highlight those with significance for lineage plasticity. We further focus on their relevance in PCa research and their benefits in PCa patient classification. Finally, we explore ways in which bioinformatic analyses can be used to determine lineage plasticity based on large omics analyses and algorithms that can shed light on upstream and downstream events. Most importantly, an integrated multiomics approach may soon allow for the identification of a lineage plasticity signature, which would revolutionize the molecular classification of PCa patients. Full article

The European mink (Mustela lutreola) is one of Europe’s most endangered species, and it is on the brink of extinction in the Iberian Peninsula. The species’ precarious situation requires the application of new ex situ conservation methodologies that complement the existing ex situ and in situ conservation measures. Here, we report for the first time the establishment of a biobank for European mink mesenchymal stem cells (emMSC) and oocytes from specimens found dead in the Iberian Peninsula, either free or in captivity. New emMSC lines were isolated from different tissues: bone marrow (emBM-MSC), oral mucosa (emOM-MSc), dermal skin (emDS-MSC), oviduct (emO-MSc), endometrium (emE-MSC), testicular (emT-MSC), and adipose tissue from two different adipose depots: subcutaneous (emSCA-MSC) and ovarian (emOA-MSC). All eight emMSC lines showed plastic adhesion, a detectable expression of characteristic markers of MSCs, and, when cultured under osteogenic and adipogenic conditions, differentiation capacity to these lineages. Additionally, we were able to keep 227 Cumulus-oocyte complexes (COCs) in the biobank, 97 of which are grade I or II. The European mink MSC and oocyte biobank will allow for the conservation of the species’ genetic variability, the application of assisted reproduction techniques, and the development of in vitro models for studying the molecular mechanisms of infectious diseases that threaten the species’ precarious situation. Full article

Bone transplantation is regarded as the preferred therapy to treat a variety of bone defects. Autologous bone tissue is often lacking at the source, and the mesenchymal stem cells (MSCs) responsible for bone repair mechanisms are extracted by invasive procedures. This study explores the potential of autologous mesenchymal stem cells derived from the hair follicle outer root sheath (MSCORS). We demonstrated that MSCORS have a remarkable capacity to differentiate in vitro towards the osteogenic lineage. Indeed, when combined with a novel gelatin-based hydrogel called Osteogel, they provided additional osteoinductive cues in vitro that may pave the way for future application in bone regeneration. MSCORS were also compared to MSCs from adipose tissue (ADMSC) and bone marrow (BMMSC) in a 3D Osteogel model. We analyzed gel plasticity, cell phenotype, cell viability, and differentiation capacity towards the osteogenic lineage by measuring alkaline phosphatase (ALP) activity, calcium deposition, and specific gene expression. The novel injectable hydrogel filled an irregularly shaped lesion in a porcine wound model displaying high plasticity. MSCORS in Osteogel showed a higher osteo-commitment in terms of calcium deposition and expression dynamics of OCN, BMP2, and PPARG when compared to ADMSC and BMMSC, whilst displaying comparable cell viability and ALP activity. In conclusion, autologous MSCORS combined with our novel gelatin-based hydrogel displayed a high capacity for differentiation towards the osteogenic lineage and are acquired by non-invasive procedures, therefore qualifying as a suitable and expandable novel approach in the field of bone regeneration therapy. Full article

In the context of aridification in Mediterranean regions, desiccation resistance and physiological plasticity will be key traits for the persistence of aquatic insects exposed to increasing desiccation stress. Control of cuticular transpiration through changes in the quantity and composition of epicuticular hydrocarbons (CHCs) is one of the main mechanisms of desiccation resistance in insects, but it remains largely unexplored in aquatic ones. We studied acclimation responses to desiccation in adults of two endemic water beetles from distant lineages living in Mediterranean intermittent saline streams: Enochrus jesusarribasi (Hydrophilidae) and Nebrioporus baeticus (Dytiscidae). Cuticular water loss and CHC composition were measured in specimens exposed to a prior non-lethal desiccation stress, allowed to recover and exposed to a subsequent desiccation treatment. E. jesusarribasi showed a beneficial acclimation response to desiccation: pre-desiccated individuals reduced cuticular water loss rate in a subsequent exposure by increasing the relative abundance of cuticular methyl-branched compounds, longer chain alkanes and branched alkanes. In contrast, N. baeticus lacked acclimation capacity for controlling water loss and therefore may have a lower physiological capacity to cope with increasing aridity. These results are relevant to understanding biochemical adaptations to drought stress in inland waters in an evolutionary and ecological context. Full article