Biology subjects

Bruneau, A.

Publications and source records attributed to Bruneau, A..

8 recordsLinked to original sources

bioRxiv2025

Identification of novel candidate regulators of human naive pluripotency by means of a genetic switch utilizing the chimeric receptor G-CSFR:GP130

This study investigated the molecular mechanisms underpinning the transition from primed to naive pluripotency in human pluripotent stem cells (hPSCs) by utilizing a dual genetic switch combining hormone-dependent STAT3-ERT2 and a chimeric GCSFR:gp130 receptor. Upon activation with tamoxifen and G-CSF, hPSCs demonstrated upregulation of naive markers, and sustained self-renewal independent of LIF. Transcriptomic analyses revealed distinct clusters of early response genes, with a subset of 26 genes significantly enriched in the human epiblast. Knockdown experiments further delineated essential regulators that modulate differentiation and proliferation during naive reprogramming including interferon gamma inducible protein (IFI)16 and interferon-induced transmembrane (IFITM) proteins. Moreover, functional assays using mutant chimeric GCSFR:gp130 receptor highlighted the critical role of JAK kinase recruitment in orchestrating epigenomic remodeling and early gene activation. This approach establishes a robust platform to dissect the signaling dynamics governing the accession of hPSCs to naive pluripotency.

cell biology↗

bioRxiv2024

Complex Reticulation in Backbone Subfamily Relationships in Leguminosae

Contradictory lines of evidence have made it difficult to resolve the phylogenetic history of the legume diversification era; this is true for the backbone topology, and for the number and timing of whole genome duplications (WGDs). By analyzing the transcriptomic data for 473 gene families in 76 species covering all six accepted legume subfamilies, we assessed the phylogenetic relationships of the legume backbone and uncovered evidence of independent whole genome duplications in each of the six legume subfamilies. Three subfamilies -- Cercidoideae, Dialioideae, and Caesalpinioideae -- bear evidence of an allopolyploid duplication pattern suggestive of ancient hybridization. In Cercidoideae and Dialioideae, the hybridization appears to be within-subfamily, with the genera Cercis and Poeppigia apparently unduplicated descendants of one of the parental lineages; in Caesalpinioideae, the hybridization appears to involve a member of the Papilionoideae lineage, and some other lineage, potentially extinct. Three independent lines of evidence, consisting of a concatenated superalignment, concordance factor analysis of the set of gene family alignments and topologies, and direct inference of reticulation events via maximum pseudo-likelihood implemented by PhyloNet, converged on a single backbone hypothesis and the above hypotheses of reticulate evolution. Significance StatementIn a hybridization event, genes that have already been evolving separately for potentially millions of years become sister chromosomes, yet remain related to one another not at the moment of hybridization, but at the speciation node of the hybrids parents. Methodologies based on counts of bursts of duplicated genes, can therefore be fundamentally vulnerable to incorrect and contradictory conclusions about the number and timing of WGD events, unless interpreted carefully and in combination with data from gene trees discordant with the consensus backbone. Our assessment of the legume backbone in that light, resolves previous contradictory findings by concluding that three legume subfamilies are allopolyploid relative to the ur-legume.

evolutionary biology↗

bioRxiv2023

Combinatory differentiation of human induced pluripotent stem cells generates thymic epithelium that supports thymic crosstalk and directs dendritic- and CD4/CD8 T-cell full development

The thymus is a primary lymphoid organ playing a crucial role in immune tolerance, by educating thymocytes through a selection mediated by thymic epithelial cells (TEC). Recent advances in gene editing and immunotherapies have made in vitro generation of iPSC-derived T cells a crucial issue with promising therapeutic applications. Current state-of-the-art approaches often fail to accurately replicate the thymic niche, resulting in impaired T cell generation, particularly for CD4+ T cells. Here we address the production of functional mature iPSc-derived TECs that are able to support in vitro T cell generation. We designed a protocol allowing iPSc differentiation into thymic epithelial progenitors (TEP) through an unbiased multifactorial method based on optimal experimental design. Modulation of signaling pathways known to regulate embryonic thymus organogenesis resulted in the obtention of TEPs expressing typical thymic markers. We achieved TEP maturation into medullary and cortical TECs by setting up a hydrogel-based 3D culture supplemented in RANK ligand, resulting in the formation of thymic organoids. To assess the functionality of the generated TECs, primary hematopoietic progenitors were co-cultured in the organoids and showed significantly improved maturation in single-positive CD4 or CD8 T cells. Remarkably, our thymic organoid model shows multilineage differentiation potential, with generation of distinct dendritic cells populations in addition to the T lineages. Thus, generation of functional TECs and thymic organoids offers a practical platform for the study of thymic cellular interactions and paves the road to future cellular therapies by producing mature thymic immune cells of clinical interest.

immunology↗

bioRxiv2022

Predicting leaf traits across functional groups using reflectance spectroscopy

O_LIPlant ecologists use functional traits to describe how plants respond to and influence their environment. Reflectance spectroscopy can provide rapid, non-destructive estimates of leaf traits, but it remains unclear whether general trait-spectra models can yield accurate estimates across functional groups and ecosystems. C_LIO_LIWe measured leaf spectra and 22 structural and chemical traits for nearly 2000 samples from 104 species. These samples span a large share of known trait variation and represent several functional groups and ecosystems. We used partial least-squares regression (PLSR) to build empirical models for estimating traits from spectra. C_LIO_LIWithin the dataset, our PLSR models predicted traits like leaf mass per area (LMA) and leaf dry matter content (LDMC) with high accuracy (R2>0.85; %RMSE<10). Models for most chemical traits, including pigments, carbon fractions, and major nutrients, showed intermediate accuracy (R2=0.55-0.85; %RMSE=12.7-19.1). Micronutrients such as Cu and Fe showed the poorest accuracy. In validation on external datasets, models for traits like LMA and LDMC performed relatively well, while carbon fractions showed steep declines in accuracy. C_LIO_LIWe provide models that produce fast, reliable estimates of several widely used functional traits from leaf reflectance spectra. Our results reinforce the potential uses of spectroscopy in monitoring plant function around the world. C_LI

ecology↗

bioRxiv2022

Precipitation is the main axis of tropical phylogenetic turnover across space and time

Early natural historians - Compte de Buffon, von Humboldt and De Candolle - established ecology and geography as two principal axes determining the distribution of groups of organisms, laying the foundations for biogeography over the subsequent 200 years, yet the relative importance of these two axes remains unresolved. Leveraging phylogenomic and global species distribution data for Mimosoid legumes, an pantropical plant clade of 3,400 species, we show that the water availability gradient from deserts to rainforests dictates turnover of lineages within continents across the tropics. We demonstrate that 95% of speciation occurs within a precipitation niche, showing profound phylogenetic niche conservatism, and that lineage turnover boundaries coincide with isohyets of precipitation. We reveal similar patterns on different continents, implying that evolution and dispersal follow universal processes.

evolutionary biology↗

bioRxiv2020

Gut microbial metabolite p-Cresol promotes autistic-like behaviors in mice through remodeling of the microbiota

BackgroundAutism Spectrum Disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis resulting in changes in microbiota composition as well as fecal, serum and urine levels of microbial metabolites. Yet, a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolite p-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice. ResultsMice exposed to p-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced by p-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further, p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred from p-Cresol-treated mice to control mice by fecal microbiota transplantation (FMT). We also showed that mice transplanted with the microbiota of p-Cresol-treated mice exhibited increased fecal p-Cresol levels compared to mice transplanted with the microbiota of control mice and identified possible p-Cresol bacterial producers. Lastly, the microbiota of control mice rescued social interactions, dopamine neurons excitability and fecal p-Cresol levels when transplanted to p-Cresol-treated mice. ConclusionsThe microbial metabolite p-Cresol induces ASD core behavioral symptoms in mice via a gut microbiota-dependent mechanism. Our study paves the way for therapeutic interventions targeting the microbiota to treat patients with ASD.

neuroscience↗

bioRxiv2019

The Origin and Early Evolution of the Legumes are a Complex Paleopolyploid Phylogenomic Tangle closely associated with the Cretaceous-Paleogene (K-Pg) Boundary

The consequences of the Cretaceous-Paleogene (K-Pg) boundary (KPB) mass extinction for the evolution of plant diversity are poorly understood, even although evolutionary turnover of plant lineages at the KPB is central to understanding the assembly of the Cenozoic biota. One aspect that has received considerable attention is the apparent concentration of whole genome duplication (WGD) events around the KPB, which may have played a role in survival and subsequent diversification of plant lineages. In order to gain new insights into the origins of Cenozoic biodiversity, we examine the origin and early evolution of the legume family, one of the most important angiosperm clades that rose to prominence after the KPB and for which multiple WGD events are found to have occurred early in its evolution. The legume family (Leguminosae or Fabaceae), with c. 20.000 species, is the third largest family of Angiospermae, and is globally widespread and second only to the grasses (Poaceae) in economic importance. Accordingly, it has been intensively studied in botanical, systematic and agronomic research, but a robust phylogenetic framework and timescale for legume evolution based on large-scale genomic sequence data is lacking, and key questions about the origin and early evolution of the family remain unresolved. We extend previous phylogenetic knowledge to gain insights into the early evolution of the family, analysing an alignment of 72 protein-coding chloroplast genes and a large set of nuclear genomic sequence data, sampling thousands of genes. We use a concatenation approach with heterogeneous models of sequence evolution to minimize inference artefacts, and evaluate support and conflict among individual nuclear gene trees with internode certainty calculations, a multi-species coalescent method, and phylogenetic supernetwork reconstruction. Using a set of 20 fossil calibrations we estimate a revised timeline of legume evolution based on a selection of genes that are both informative and evolving in an approximately clock-like fashion. We find that the root of the family is particularly difficult to resolve, with strong conflict among gene trees suggesting incomplete lineage sorting and/or reticulation. Mapping of duplications in gene family trees suggest that a WGD event occurred along the stem of the family and is shared by all legumes, with additional nested WGDs subtending subfamilies Papilionoideae and Detarioideae. We propose that the difficulty of resolving the root of the family is caused by a combination of ancient polyploidy and an alternation of long and very short internodes, shaped respectively by extinction and rapid divergence. Our results show that the crown age of the legumes dates back to the Maastrichtian or Paleocene and suggests that it is most likely close to the KPB. We conclude that the origin and early evolution of the legumes followed a complex history, in which multiple nested polyploidy events coupled with rapid diversification are associated with the mass extinction event at the KPB, ultimately underpinning the evolutionary success of the Leguminosae in the Cenozoic.

evolutionary biology↗

bioRxiv2019

Phylogenomics within the Anthonotha clade (Detarioideae, Leguminosae) reveals a high diversity in floral trait shifts and a general trend towards organ number reduction

Detarioideae is well known for its high diversity of floral traits, including flower symmetry, number of organs, and petal size and morphology. This diversity has been characterized and studied at higher taxonomic levels, but limited analyses have been performed among closely related genera with contrasting floral traits due to the lack of fully resolved phylogenetic relationships. Here, we used four representative transcriptomes to develop an exome capture bait for the entire subfamily and applied it to the Anthonotha clade using a complete data set (61 specimens) representing all extant floral diversity. Our phylogenetic analyses recovered congruent topologies using ML and Bayesian methods. The genus Anthonotha was recovered as monophyletic contrary to the remaining three genera (Englerodendron, Isomacrolobium and Pseudomacrolobium), which form a monophyletic group sister to Anthonotha. We inferred a total of 35 transitions for the seven floral traits (pertaining to flower symmetry, petals, stamens and staminodes) that we analyzed, suggesting that at least 30% of the species in this group display transitions from the ancestral condition reconstructed for the Anthonotha clade. The main transitions were towards a reduction in the number of organs (petals, stamens and staminodes). Despite the high number of transitions, our analyses indicate that the seven characters are evolving independently in these lineages. Petal morphology is the most labile floral trait with a total of seven independent transitions in number and seven independent transitions to modification in petal types. The diverse petal morphology along the dorsoventral axis of symmetry within the flower is not associated with differences at the micromorphology of petal surface, suggesting that in this group all petals within the flower might possess the same petal identity at the molecular level. Our results provide a solid evolutionary framework for further detailed analyses of the molecular basis of petal identity.

evolutionary biology↗