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Biology subjects

Campos, L.

Publications and source records attributed to Campos, L..

8 recordsLinked to original sources

Mechanical cues from muscle contraction regulate TGFβ signaling and epitenon formation during embryonic tendon development.

Muscle loading is required for embryonic tendon growth; however, the underlying mechanisms that regulate tendon development downstream of mechanical cues remain unidentified. Although tendons in muscle paralysis models are structurally and functionally inferior, whether these differences arise from cell or matrix deficits remains unclear. Analysis of muscular dysgenesis embryos by atomic force microscopy showed that structural and functional deficits in paralyzed tendon arise in part from reduced proliferation and collagen fibril disorganization. Bulk and single cell transcriptional analyses reveal that both collagenous and non-collagenous extracellular matrix components, as well as cytoskeletal and actomyosin-associated proteins, are dysregulated in mdg tendons, whereas tendon markers remain unchanged. Surprisingly, we find that an arrest of TGF{beta} signaling occurs during normal embryonic tendon growth and that TGF{beta} signaling is abnormally prolonged in paralyzed embryos. We also show for the first time, that specification of the epitenon depends on muscle contraction. Together, these findings establish cell and molecular requirements for muscle contraction in embryonic tendon development. TeaserMuscle contraction is required for embryonic tendon development through regulation of TGF{beta} signaling, epitenon formation, and matrix organization.

developmental biology↗

Neural Dynamics Underlying Repeated Learning of Visual Image Sequences

Humans possess a remarkable ability to recognize visual objects with high fidelity, supported by complex neural mechanisms underlying memory retrieval. Event-related potential (ERP) studies have identified two key neural signatures of recognition memory: the parietal old/new effect and the frontal old/new effect. Despite extensive research on these ERP components, the extent to which these components reflect distinct memory processes remains debated. In the present study, we investigated how repetitive learning modulates these ERP components. Participants repeatedly studied a fixed list of 32 real-world images across up to five study-test repetitions while EEG was recorded. Additionally, a separate set size 1 condition served as a proxy for working memory. Our results showed that with increased repetitions, the parietal old/new effect exhibited enhanced amplitude and earlier peak latency, reflecting more efficient retrieval of well-learned memories. In contrast, the frontal old/new effect remained unchanged in both amplitude and timing. These findings suggest that the parietal old/new effect is a sensitive neural marker of learning-related changes in long-term memory representations, while the frontal effect is less influenced by repetition. Additionally, despite similarly high accuracy between the well-practiced set size 32 condition and the set size 1 working memory condition, both parietal and frontal old/new effects peaked significantly earlier for set size 1, suggesting that access to working memory is substantially faster than even well-practiced long-term memory. Together, our results highlight the unique role of the parietal old/new effect, but not the frontal old/new effect, in repetitive learning, despite both components being important for successful recognition of learnt visual stimuli.

neuroscience↗

Dynamic cell fate plasticity and tissue integration drive functional synovial joint regeneration

Adult mammalian synovial joints have limited regenerative capacity, where injuries heal with mechanically inferior fibrotic tissues. Here we developed a unilateral whole-joint resection model in adult zebrafish to advance our understanding of how to stimulate regrowth of native synovial joint tissues. Using a combination of microCT, histological, live imaging, and single-cell RNA sequencing (scRNAseq) approaches after complete removal of all joint tissues, we find de novo regeneration of articular cartilage, ligament, and synovium into a functional joint. Clonal lineage tracing and scRNAseq implicate a multipotent, neural crest-derived population in the adult skeleton as a cell source for these regenerating tissues. Together, our findings reveal latent molecular and cellular programs within the adult skeleton that are deployed to regenerate a complex joint with lubricated articular cartilage.

developmental biology↗

Metabolic crosstalk between hydroxylated monoterpenes and salicylic acid in tomato defence response against Pseudomonas syringae pv tomato

Hydroxylated monoterpenes (HMTPs) are differentially emitted by tomato plants efficiently resisting a bacterial infection. We have studied the defensive role of these volatiles in the tomato response to bacteria, whose main entrance are stomata apertures. Treatments with some HMTPs resulted in stomatal closure and PR1 induction. Particularly, -terpineol induced stomatal closure in a salicylic (SA) and abscisic acid-independent manner, and conferred resistance to bacteria. Interestingly, transgenic tomato plants overexpressing or silencing the monoterpene synthase MTS1, which displayed alterations in the emission of HMTPs, exhibited changes in the stomatal aperture but not in plant resistance. Measures of both 2-C-methyl-D-erythritol-2,4-cyclopyrophosphate (MEcPP) and SA levels, revealed a competition for MEcPP by the methylerythritol phosphate (MEP) pathway and the SA biosynthesis activation, thus explaining the absence of phenotype in transgenic plants. These results were confirmed by chemical inhibition or activation of the MEP pathway. Besides, treatments with BTH, a SA functional analogue, conferred enhanced resistance in transgenic tomato plants overexpressing MTS1. Finally, plants overexpressing MTS1 induced PR1 and stomata closure in neighbouring plants. Our results confirm the role of HMTPs in both intra and inter-plant immune signalling, and reveal a metabolic crosstalk between the MEP and SA pathways in tomato plants. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/539605v2_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@1048cddorg.highwire.dtl.DTLVardef@1bc1948org.highwire.dtl.DTLVardef@1ff0eaorg.highwire.dtl.DTLVardef@101c4fa_HPS_FORMAT_FIGEXP M_FIG Metabolic crosstalk between hydroxylated monoterpenes and salicylic acid in tomato defence response against Pseudomonas syringae pv tomato. Created with BioRender.com. C_FIG

plant biology↗

SlS5H silencing reveals specific pathogen-triggered salicylic acid metabolism in tomato

The phytohormone salicylic acid (SA or 2-hydroxybenzoic acid) plays an important role in plant biotic and abiotic responses. Gentisic acid (GA or 2,5-Dihydroxybenzoic acid, 2,5-DHBA) is the product of the SA 5-hydroxylation which is catalysed by the S5H enzyme, also known as DMR6. GA has been described to accumulate at high levels in compatible plant-pathogen interactions such as tomato plants infected by Citrus Exocortis Viroid (CEVd), and to a much lesser extend upon Pseudomonas syringae DC3000 pv. tomato (Pst) infection. Here we describe the specific effect that tomato SlS5H impairment produces on both plant-pathogen interactions. The induction of SlS5H in tomato plants by different pathogens was corroborated by qRT-PCR and correlated with previously described 2,5-DHBA accumulations. Transient SlS5H over-expression assays in Nicotiana benthamiana confirmed that SA is a substrate for SlS5H in vivo. RNAi_SlS5H tomato transgenic plants were generated and characterized upon CEVd and Pst infections. Transgenic tomato plants displayed an activation of defences and therefore a loss of susceptibility against both pathogens, and alternative SA homeostasis seems to occur for each specific interaction. Metabolomic assays revealed that whilst the glycosylated form of SA was the most discriminant metabolite found in CEVd infected RNAi_SlS5H transgenic plants, trans-feruloyldopamine, feruloylquinic acid, feruloylgalactarate and 2-hydroxyglutarate were the most accumulated compounds in the Pst-infected transgenic tomato leaves. Transgenic lines also displayed hyper susceptibility to Botrytis cinerea, as well as a smaller size and early senescence. Collectively, our results reveal a novel mechanism by which tomato plants specifically set SA homeostasis upon different pathogen attacks. One sentence summaryThe impairment of SA hydroxylation in tomato plants uncovers specific SA homeostasis upon CEVd or Pseudomonas syringae infections.

biochemistry↗

Cross-tissue immune cell analysis reveals tissue-specific adaptations and clonal architecture across the human body

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. Here, we surveyed the immune compartment of 15 tissues of six deceased adult donors by single-cell RNA sequencing and paired VDJ sequencing. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of 45 finely phenotyped immune cell types and states, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. In summary, our multi-tissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis and antigen receptor sequencing. One Sentence SummaryWe provide an immune cell atlas, including antigen receptor repertoire profiling, across lymphoid and non-lymphoid human tissues.

immunology↗

Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated single-cell and spatial reference maps of the human uterus and 3D endometrial organoid cultures. We dissect the signalling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids highlights common pathways regulating the differentiation of secretory and ciliated lineage in vivo and in vitro. We show in vitro that downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. These mechanistic insights provide a platform for future development of treatments for a range of common endometrial disorders including endometriosis and carcinoma.

genomics↗

Establishment In Culture Of Expanded Potential Stem Cells

Mouse embryonic stem cells are derived from in vitro explantation of blastocyst epiblasts1,2 and contribute to both the somatic lineage and germline when returned to the blastocyst3 but are normally excluded from the trophoblast lineage and primitive endoderm4-6. Here, we report that cultures of expanded potential stem cells (EPSCs) can be established from individual blastomeres, by direct conversion of mouse embryonic stem cells (ESCs) and by genetically reprogramming somatic cells. Remarkably, a single EPSC contributes to the embryo proper and placenta trophoblasts in chimeras. Critically, culturing EPSCs in a trophoblast stem cell (TSC) culture condition permits direct establishment of TSC lines without genetic modification. Molecular analyses including single cell RNA-seq reveal that EPSCs share cardinal pluripotency features with ESCs but have an enriched blastomere transcriptomic signature and a dynamic DNA methylome. These proof-of-concept results open up the possibility of establishing cultures of similar stem cells in other mammalian species.

developmental biology↗