Biology subjects

Valbuena, R.

Publications and source records attributed to Valbuena, R..

8 recordsLinked to original sources

bioRxiv2026

Broadleaved hedgerows as complementary habitats for small mammals in pine plantation landscapes

O_LIThe global decline of natural forests is accompanied by a rapid expansion of commercial tree plantations, which are expected to further increase to meet growing demand for wood products. However, planted forests generally support lower biodiversity than natural forests, particularly when monospecific and intensively managed. In this context, broadleaved hedgerows have been proposed as a nature-based solution to enhance biodiversity within conifer-dominated plantation landscapes. Such features may be especially beneficial for small mammals, including rodents and shrews, which are key contributors to forest ecosystem functioning. However, their effects on small mammal communities remain largely unquantified. C_LIO_LIHere, we assessed variation in small mammal communities among habitat types within a native pine plantation-dominated landscape in southwestern France. Using a multi-year, multi-season survey, we compared species richness and abundance among plantation edges, broadleaved hedgerows embedded within plantations and natural broadleaved forests. We further tested whether environmental descriptors of hedgerow sites influenced dominant species and whether seasonal and interannual demographic dynamics modified habitat-related patterns. C_LIO_LIPine plantation edges and broadleaved hedgerows supported lower small mammal species richness than natural broadleaved forests and were dominated by two habitat generalists, Apodemus sylvaticus and Crocidura russula. This pattern was driven by the near absence of the forest specialist Clethrionomys glareolus. Hedgerows did not increase species richness relative to plantations, but provided favourable habitat for A. sylvaticus, which was scarce in pine plantation, while supporting fewer C. russula. Variation in hedgerow structure and composition further influenced A. sylvaticus abundance, while seasonal and interannual rodent population dynamics modulated habitat-related differences. C_LIO_LIOur results indicate that intensively managed pine plantations act as environmental filters, excluding forest-associated small mammals. While broadleaved hedgerows benefited one species, their capacity to restore forest-specialist communities was limited without broader landscape-scale interventions. These findings highlight both the ecological benefits and constraints of edge-based habitat interventions and provide guidance for designing and evaluating biodiversity-oriented management in plantation landscapes. C_LI

ecology↗

bioRxiv2025

An image-based CRISPR screen reveals splicing-mediated control of HP1α condensates

Heterochromatin Protein 1 (HP1) is a fundamental component of constitutive heterochromatin, forming subnuclear condensates whose regulation and function remain poorly understood. Here, we present an image-based CRISPR screen targeting nuclear factors that identifies splicing as a pivotal pathway regulating HP1 condensates. We discovered that unspliced intronic RNA modulates HP1 condensates by interacting co-transcriptionally with HP1. By modulating the intron content, RNA processing restricts HP1-RNA interactions at chromatin, thus enabling heterochromatin organization. Disruption of HP1 condensates due to enhanced interactions with unspliced RNA leads to loss of heterochromatin and the activation of stress response protective genes. We propose that RNA is a central component of heterochromatin that modulates HP1 condensates, and that RNA processing enzymes act as a surveillance mechanism for condensates by dynamically regulating the network of multi-valent interactions between RNA and chromatin factors. This model underscores the crosstalk between chromatin organization, transcription, and RNA processing, potentially governing broader nuclear functions.

genetics↗

bioRxiv2025

Clonal lineage tracing of innate immune cells in human cancer

Innate immune cells constitute the majority of the tumor microenvironment (TME), where they mediate both natural anti-tumor immunity and immunotherapy responses. While single-cell T- and B-cell receptor sequencing has provided fundamental insights into the clonal dynamics of human adaptive immunity, the lack of appropriate tools has precluded similar analysis of innate immune cells. Here, we describe a method that leverages somatic mitochondrial DNA (mtDNA) mutations to reconstruct clonal lineage relationships between single cells across cell types in native human tissues. We jointly sequenced single-cell transposase-accessible chromatin and mtDNA to profile n=124,958 cells from matched tumor, non-involved lung tissue (NILT), and peripheral blood of early-stage non-small cell lung cancer (NSCLC) patients, as well as n=93,757 cells from matched tumor and peripheral blood of ovarian cancer patients. Single-cell concomitant profiling of lineage and cell states of thousands of immune cells resolved clonality across cell types, tissue sites, and malignancies. Clonal tracing of innate immune cells demonstrates that TME-resident myeloid subsets, including macrophages and type 3 dendritic cells (DC3), are clonally linked to both circulating and tissue-infiltrating monocytes. Further, we identify distinct DC-biased and macrophage-biased myeloid clones, enriched in the tumor and NILT, respectively, and find that their circulating monocyte precursors exhibit distinct epigenetic profiles, suggesting that myeloid differentiation fate may be predetermined before TME infiltration. These results delineate the clonal pathways of intratumoral myeloid cell recruitment and differentiation in human cancer and suggest that remodeling of the tumor myeloid compartment may be peripherally programmed.

genomics↗

bioRxiv2024

Prediction and design of transcriptional repressor domains with large-scale mutational scans and deep learning

Regulatory proteins have evolved diverse repressor domains (RDs) to enable precise context-specific repression of transcription. However, our understanding of how sequence variation impacts the functional activity of RDs is limited. To address this gap, we generated a high-throughput mutational scanning dataset measuring the repressor activity of 115,000 variant sequences spanning more than 50 RDs in human cells. We identified thousands of clinical variants with loss or gain of repressor function, including TWIST1 HLH variants associated with Saethre-Chotzen syndrome and MECP2 domain variants associated with Rett syndrome. We also leveraged these data to annotate short linear interacting motifs (SLiMs) that are critical for repression in disordered RDs. Then, we designed a deep learning model called TENet (Transcriptional Effector Network) that integrates sequence, structure and biochemical representations of sequence variants to accurately predict repressor activity. We systematically tested generalization within and across domains with varying homology using the mutational scanning dataset. Finally, we employed TENet within a directed evolution sequence editing framework to tune the activity of both structured and disordered RDs and experimentally test thousands of designs. Our work highlights critical considerations for future dataset design and model training strategies to improve functional variant prioritization and precision design of synthetic regulatory proteins.

genomics↗

bioRxiv2023

Mapping ovarian cancer spatial organization uncovers immune evasion drivers at the genetic, cellular, and tissue level

Immune exclusion and evasion are central barriers to the success of immunotherapies and cell therapies in solid tumors. Here we applied single cell spatial and perturbational transcriptomics alongside clinical, histological, and genomic profiling to elucidate immune exclusion and evasion in high-grade serous tubo-ovarian cancer (HGSC). Using high-plex spatial transcriptomics we profiled more than 1.3 million cells from 95 tumors and 60 patients, revealing generalizable principles in HGSC tumor tissue organization. Our data demonstrates that effector T cells resist stroma-mediated trapping and sequestration. However, upon infiltration into the tumor, T cells, as well as Natural Killer (NK) cells, preferentially co-localize only with a subset of malignant cells that manifest a distinct transcriptional cell state. The latter consists of dozens of co-regulated genes and is repressed under various copy number alterations. Performing CRISPR Perturb-seq screens in ovarian cancer cells, we identified functionally diverse genetic perturbations - including knockout of the insulin sensing repressor PTPN1 and the epigenetic regulator ACTR8 - that de-repress the proposed immunogenic malignant cell state identified in patients and indeed sensitize ovarian cancer cells to T cell and NK cell cytotoxicity. Taken together, our study uncovered a profound connection between somatic genetic aberrations, malignant cell transcriptional dysregulation, and immune evasion at the cellular and tissue level, allowing us to identify targets that reprogram malignant cell states as an avenue to unleash anti-tumor immune responses.

cancer biology↗

bioRxiv2023

Plant allometry derived from Metabolic Scaling Theory and segregated by tissue functionality

Plant allometry is key for determining the role of forests in global carbon cycles, through the calculation of tree biomass using proxy measurements such as tree diameters or heights. Metabolic Scaling Theory (MST) considers the general principles that underpin allometry, but MST scaling relationships have been challenged on their lack of fit to empirical data and global applicability. Many authors have thus optimised their model forms for statistical performance over theory based approaches. We postulated that MST scaling is applicable only to the proportion of plant tissue with supportive functionality, meaning that as plants evolved tissues of specialized conductive functionality (e.g vessels) their allometry progressed into more complex relationships. Our generalised MST (gMST) models were thus created by considering conductive lumen as unsupportive area, and consequentially removing it from the original MST 2/3 scaling. According to this principle, we deducted generalized gMST relationships with mechanistically deducted coefficients. We found that the gMST height-diameter scaling outperformed current state of the art equations that are widely used within the tropics and that the model performed well across all tested ecoregions. Furthermore, the proposed aboveground biomass models performed similarly to widely used models in the literature within the tropics. The results presented indicate that the further development of generalised allo-metric models remains a research priority given the importance of assessing and monitoring global forest carbon fluxes. The height-diameter models presented can thus be of much use to the wider community in further refining carbon stock estimates globally, providing a universally applicable theoretical framework.

plant biology↗

bioRxiv2021

Klf5 establishes bi-potential cell fate by dual regulation of ICM and TE specification genes

Early blastomeres of mouse preimplantation embryos exhibit bi-potential cell fate, capable of generating both embryonic and extra-embryonic lineages in blastocysts. Here, we identified three major 2 cell (2C) specific endogenous retroviruses (ERVs) as the molecular hallmark of the bi-potential plasticity. Using the LTRs of all three 2C-ERVs, we identified Klf5 as their major upstream regulator. Klf5 is essential for bi-potential cell fate: a single Klf5-overexpressing ESC generated terminally differentiated embryonic and extra-embryonic lineages in chimeric embryos, and Klf5 directly induces both ICM and TE specification genes. Intriguingly, Klf5 and Klf4 act redundantly during ICM specification, whereas Klf5 deficiency alone impairs TE specification. Klf5 is regulated by multiple 2C-specific transcription factors, particularly Dux, and the Dux/Klf5 axis is evolutionarily conserved. Altogether, the 2C-specific transcription program converges on Klf5 to establish bi-potential cell fate, enabling a cell state with dual activation of ICM and TE genes.

developmental biology↗

bioRxiv2020

Resource availability and availability and disturbance shape maximum tree height across the Amazon

The factors shaping the distribution of giant tropical trees are poorly understood, despite its importance as a link between evolutionary biology and ecosystem biogeochemistry. The recent discovery of clusters of trees over 80 metres tall in the Guiana Shield region of the Amazon rainforest challenges the current understanding of the factors controlling the growth and survival of giant trees. The new discovery led us to revisit the question: what determines the distribution of the tallest trees of the Amazon? Here, we used high-resolution airborne LiDAR (Light Detection and Ranging) surveys to measure canopy height across 282,750 ha of primary old-growth and secondary forests throughout the entire Brazilian Amazon to investigate the relationship between the occurrence of giant trees and the environmental factors that influence their growth and survival. Our results suggest that the factors controlling where trees grow extremely tall are distinct from those controlling their longevity. Trees grow taller in areas with high soil clay content (> 42%), lower radiation (< 130 clear days per year) and wind speeds, avoiding alluvial areas (elevations higher than 40 m a.s.l), and with an optimal precipitation range of 1,500 to 2,500 mm yr-1. We then used an envelope model to determine the environmental conditions that support the very tallest trees (i.e. over 70 m height). We found that, as opposed to the myriad of interacting factors that control the maximum height at a large scale, wind speed had by far the largest influence on the distribution of these sentinel trees, and explained 67% of the probability of finding trees over 70 m in the Brazilian Amazon forest. The high-resolution pan-Amazon LiDAR data showed that environmental variables that drive growth in height are fundamentally different from environmental variables that support their survival. While precipitation and temperature seem to have lower importance for their survival than expected from previous studies, changes in wind and radiation regimes could reshape our forested biomes. This should be carefully considered by policy-makers when identifying important hotspots for the conservation of biodiversity in the Amazon.

ecology↗