Biology subjects

Silva, J. C. R.

Publications and source records attributed to Silva, J. C. R..

6 recordsLinked to original sources

bioRxiv2025

Fueling a predator death-trap: Trophic subsidies and the risk of management-induced collapse in a predator-prey system

O_LIAnthropogenic subsidies create complex ecological dynamics, yet their interaction with invasive species management is poorly understood. Managing subsidies or predators in isolation risks perverse outcomes, including population collapses, demanding a more holistic understanding. C_LIO_LIWe employed a Pattern-Oriented Inference framework to synthesize multiple lines of evidence for the endemic Noronha skink (Trachylepis atlantica) across an archipelago. We analyzed three key patterns using complementary methods: (i) population density, estimated via capture-mark-recapture and negative binomial GLMs of count data; (ii) individual body size, using gamma GLMs; and (iii) injury rates, via tail-autotomy analysis. C_LIO_LIWe documented a dramatic density gradient driven by predation pressure. Skink populations were over three times denser on predator-light secondary islands (0.411 ind/m2, 95% CI: 0.297-0.568) than in predator-rich PARNAMAR (0.125 ind/m2, 95% CI: 0.090-0.174). Although anthropogenic subsidies boosted density by 82% in the inhabited APA (0.227 ind/m2, 95% CI: 0.174-0.297), this was insufficient to overcome the severe impact of invasive predators. C_LIO_LIThis created a paradox where density, a traditional population success metric, was inverse to size, an indicator of individual fitness. On the main island, although the subsidized APA was denser than PARNAMAR, individual condition was no better. Adult males in the APA were as small as those in the lowest-density sites and significantly smaller than males on the secondary islands. Predation pressure explains this gradient, with tail-loss injury rates peaking in the APA (29.3%), remaining high in PARNA (25.0%), and dropping about 50% on the secondary islands (15.0%). C_LIO_LISynthesis and applications: The convergence of these patterns supports a "predator death-trap" hypothesis, where trophic subsidies in the inhabited APA fuel high skink recruitment, masking extreme mortality from a subsidized predator community and other anthropogenic threats. This dynamic produces high population turnover and truncates size structure by selectively removing larger, older adults and may explain patterns seen elsewhere. Our findings have critical management implications: removing food subsidies without concurrent, effective control of key invasive predators could trigger a population collapse. We advocate integrated, multi-species management and provide robust evidence for the threatened status of this endemic reptile. C_LI

ecology↗

bioRxiv2024

Chemically induced cell plasticity enables the generation of high-fidelity embryo model

Embryo models open exciting opportunities for improving our understanding of development and advancing medicine. However, current models depend on intricate procedures and the integration of separately generated cell types. Here, we aimed to establish a chemical-only strategy to induce cellular plasticity and generate embryo founder-like cells. Within 60 hours, chemical-induced pluripotent stem cells activated early lineage specifiers, Cdx2 and Gata6, while maintaining Oct4/ Pou5f1 expression. Following a second 36-hour chemical treatment, founder-like cells developed into all blastocyst fates and self-assembled into embryo-like structures. These progressed into high-fidelity late-streak gastrulation stages within 4.5 days, displaying primitive streak formation via epithelial-to-mesenchymal transition, along with germ-layer tissues, amnion, and ectoplacental cone. Fate trajectories and molecular signatures from founder-like cells to chemically-induced embryo model (ci-MO) were defined, revealing remarkable similarity up to Embryonic day (E) 7.5 embryo. Summarily, ci-MO offers a straightforward, rapid, small-molecule-only, and high-fidelity approach to study embryonic development and cell fate specification. HighlightsO_LIGeneration of a direct, efficient, and sophisticated chemically induced embryo model (ci-MO) C_LIO_LITwo-pulse chemical induction reprograms ESCs into founder-like cells capable of developing all embryo fates C_LIO_LIGastrulating ci-MOs display high morphological and molecular accuracy C_LIO_LIci-MOs reconstruct embryo developmental trajectories C_LI

cell biology↗

bioRxiv2020

Auxin-degron system identifies immediate mechanisms of Oct4

The pluripotency factor Oct4 is essential for the maintenance of naive pluripotent stem cells in vitro and in vivo. However, the specific role of Oct4 in this process remains unknown. Here, we developed a rapid protein-level Oct4 depletion system that demonstrates that the immediate downstream response to loss of Oct4 is reduced expression of key pluripotency factors. Our data show a requirement for Oct4 for the efficient transcription of several key pluripotency factors, and suggest that expression of trophectoderm markers is a subsequent event. Additionally, we find that Nanog is competent to bind to the genome in the absence of Oct4, and this binding is in fact enhanced. Globally, however, active enhancer associated histone mark H3K27ac is depleted. Our work establishes that while Oct4 is required for the maintenance of the naive transcription factor network, at a normal ESC level it antagonises this network through inhibition of Nanog binding.

developmental biology↗

bioRxiv2020

Sox2 modulation increases naive pluripotency plasticity

Induced pluripotency provides a tool to explore the molecular mechanisms underlying the establishment, maintenance and differentiation of naive pluripotent stem cells (nPSCs). Here, we report that self-renewal of nPSCs requires minimal Sox2 expression (Sox2-low). Sox2-low nPSCs do not show impaired neuroectoderm specification and differentiate efficiently in vitro into all embryonic germ lineages. Strikingly, Sox2-low cells also differentiate towards the trophoblast lineage both in vitro and in vivo. At the single-cell level self-renewing Sox2-low nPSCs exhibit a homogeneous naive molecular signature. However, they also display a basal trophoblast molecular signature and decreased ability of Oct4 to bind naive-associated regulatory sequences compared to control cells. These features underlie observed enhanced cell potency upon the removal of self-renewing cues. In sum, this work defines Sox2 as a restrictor of developmental potential and suggests perturbation of the naive pluripotent network as an underlying cause of increased cell potency. HighlightsO_LILow Sox2 expression is sufficient for naive pluripotent stem cell self-renewal C_LIO_LILow Sox2 expression does not impair neurectoderm differentiation in vitro C_LIO_LILow Sox2 expression impairs Oct4 genomic occupancy C_LIO_LILow Sox2 expression increases naive pluripotent cell plasticity in vitro and in vivo C_LI

developmental biology↗

bioRxiv2019

StemBond hydrogels optimise the mechanical microenvironment for embryonic stem cells

Studies of mechanical signalling are typically performed by comparing cells cultured on soft and stiff hydrogel-based substrates. However, it is challenging to independently and robustly control both substrate stiffness and tethering of extracellular matrix (ECM) to substrates, making ECM tethering a potentially confounding variable in mechanical signalling investigations. Moreover, poor ECM tethering can lead to weak cell attachment. To address this, we developed StemBond hydrogels, a hydrogel formulation in which ECM tethering is stable and can be varied independently of stiffness. We show that soft StemBond hydrogels provide an optimal format for culturing embryonic stem (ES) cells. We find that soft StemBond substrates improve the homogeneity of ES cell populations, boost their self-renewal, and increase the efficiency of cellular reprogramming. Our findings underline how soft microenvironments impact mechanosensitive signalling pathways regulating self-renewal and differentiation, indicating that optimising the complete mechanical microenvironment will offer greater control over stem cell fate specification.

cell biology↗

bioRxiv2018

Wdr5, Brca1 and Bard1 link the DNA damage response to the mesenchymal-to-epithelial transition during early reprogramming.

Differentiated cells are epigenetically stable, but can be reprogrammed to pluripotency by expression of the OSKM transcription factors. Despite significant effort, relatively little is known about the cellular requirements for reprogramming and how they affect the properties of induced pluripotent stem cells (iPSC). We have performed high-content screening with siRNAs targeting 300 chromatin-associated factors. We used colony features, such as size and shape, as well as strength and homogeneity of marker gene expression to define five colony phenotypes in early reprogramming. We identified transcriptional signatures associated with these phenotypes in a secondary RNA sequencing screen. One of these phenotypes involves large colonies and an early block of reprogramming. Double knockdown epistasis experiments of the genes involved, revealed that Brca1, Bard1 and Wdr5 functionally interact and are required for both the DNA damage response and the mesenchymal-to-epithelial transition (MET), linking these processes. Moreover, the data provide a resource on the role of chromatin-associated factors in reprogramming and underline colony morphology as an important high dimensional readout for reprogramming quality.

developmental biology↗