Prolonged dysbiosis and altered immunity under nutritional intervention in a physiological mouse model of severe acute malnutrition.

Severe acute malnutrition (SAM) is a multifactorial disease affecting millions of children worldwide. It is associated with changes in intestinal physiology, microbiota, and mucosal immunity, emphasizing the need for multidisciplinary studies to unravel its full pathogenesis. We established an experimental model in which weanling mice fed a high-deficiency diet mimic key anthropometric and physiological features of SAM in children. This diet alters the intestinal microbiota (less segmented filamentous bacteria, spatial proximity to epithelium), metabolism (decreased butyrate), and immune cell populations (depletion of LysoDC in Peyer's patches and intestinal Th17 cells). A nutritional intervention leads to a fast zoometric and intestinal physiology recovery but to an incomplete restoration of the intestinal microbiota, metabolism, and immune system. Altogether, we provide a preclinical model of SAM and have identified key markers to target with future interventions during the education of the immune system to improve SAM whole defects.

Epithelial disruption drives mesendoderm differentiation in human pluripotent stem cells by enabling TGF-ß protein sensing.

The processes of primitive streak formation and fate specification in the mammalian epiblast rely on complex interactions between morphogens and tissue organization. Little is known about how these instructive cues functionally interact to regulate gastrulation. We interrogated the interplay between tissue organization and morphogens by using human induced pluripotent stem cells (hiPSCs) downregulated for the morphogen regulator GLYPICAN-4, in which defects in tight junctions result in areas of disrupted epithelial integrity. Remarkably, this phenotype does not affect hiPSC stemness, but impacts on cell fate acquisition. Strikingly, cells within disrupted areas become competent to perceive the gastrulation signals BMP4 and ACTIVIN A, an in vitro surrogate for NODAL, and thus differentiate into mesendoderm. Yet, disruption of epithelial integrity sustains activation of BMP4 and ACTIVIN A downstream effectors and correlates with enhanced hiPSC endoderm/mesoderm differentiation. Altogether, our results disclose epithelial integrity as a key determinant of TGF-ß activity and highlight an additional mechanism guiding morphogen sensing and spatial cell fate change within an epithelium.

Genomic evidence for global ocean plankton biogeography shaped by large-scale current systems.

Biogeographical studies have traditionally focused on readily visible organisms, but recent technological advances are enabling analyses of the large-scale distribution of microscopic organisms, whose biogeographical patterns have long been debated. Here we assessed the global structure of plankton geography and its relation to the biological, chemical, and physical context of the ocean (the 'seascape') by analyzing metagenomes of plankton communities sampled across oceans during the Tara Oceans expedition, in light of environmental data and ocean current transport. Using a consistent approach across organismal sizes that provides unprecedented resolution to measure changes in genomic composition between communities, we report a pan-ocean, size-dependent plankton biogeography overlying regional heterogeneity. We found robust evidence for a basin-scale impact of transport by ocean currents on plankton biogeography, and on a characteristic timescale of community dynamics going beyond simple seasonality or life history transitions of plankton.

Oceans are brimming with life invisible to our eyes, a myriad of species of bacteria, viruses and other microscopic organisms essential for the health of the planet. These 'marine plankton' are unable to swim against currents and should therefore be constantly on the move, yet previous studies have suggested that distinct species of plankton may in fact inhabit different oceanic regions. However, proving this theory has been challenging; collecting plankton is logistically difficult, and it is often impossible to distinguish between species simply by examining them under a microscope. However, within the last decade, a research schooner called Tara has travelled the globe to gather thousands of plankton samples. At the same time, advances in genomics have made it possible to identify species based only on fragments of their DNA sequence. To understand the hidden geography of plankton communities in Earth's oceans, Richter et al. pored over DNA from the Tara Oceans expedition. This revealed that, despite being unable to resist the flow of water, various planktonic species which live close to the surface manage to occupy distinct, stable provinces shaped by currents. Different sizes of plankton are distributed in different sized provinces, with the smallest organisms tending to inhabit the smallest areas. Comparing DNA similarities and speeds of currents at the ocean surface revealed how these might stretch and mix plankton communities. Plankton play a critical role in the health of the ocean and the chemical cycles of planet Earth. These results could allow deeper investigation by marine modellers, ecologists, and evolutionary biologists. Meanwhile, work is already underway to investigate how climate change might impact this hidden geography.

Specialization of actin isoforms derived from the loss of key interactions with regulatory factors.

A paradox of eukaryotic cells is that while some species assemble a complex actin cytoskeleton from a single ortholog, other species utilize a greater diversity of actin isoforms. The physiological consequences of using different actin isoforms, and the molecular mechanisms by which highly conserved actin isoforms are segregated into distinct networks, are poorly known. Here, we sought to understand how a simple biological system, composed of a unique actin and a limited set of actin-binding proteins, reacts to a switch to heterologous actin expression. Using yeast as a model system and biomimetic assays, we show that such perturbation causes drastic reorganization of the actin cytoskeleton. Our results indicate that defective interaction of a heterologous actin for important regulators of actin assembly limits certain actin assembly pathways while reinforcing others. Expression of two heterologous actin variants, each specialized in assembling a different network, rescues cytoskeletal organization and confers resistance to external perturbation. Hence, while species using a unique actin have homeostatic actin networks, actin assembly pathways in species using several actin isoforms may act more independently.

Genome Resolved Biogeography of Mamiellales.

Among marine phytoplankton, Mamiellales encompass several species from the genera Micromonas, Ostreococcus and Bathycoccus, which are important contributors to primary production. Previous studies based on single gene markers described their wide geographical distribution but led to discussion because of the uneven taxonomic resolution of the method. Here, we leverage genome sequences for six Mamiellales species, two from each genus Micromonas, Ostreococcus and Bathycoccus, to investigate their distribution across 133 stations sampled during the Tara Oceans expedition. Our study confirms the cosmopolitan distribution of Mamiellales and further suggests non-random distribution of species, with two triplets of co-occurring genomes associated with different temperatures: Ostreococcuslucimarinus, Bathycoccusprasinos and Micromonaspusilla were found in colder waters, whereas Ostreococcus spp. RCC809, Bathycoccus spp. TOSAG39-1 and Micromonascommoda were more abundant in warmer conditions. We also report the distribution of the two candidate mating-types of Ostreococcus for which the frequency of sexual reproduction was previously assumed to be very low. Indeed, both mating types were systematically detected together in agreement with either frequent sexual reproduction or the high prevalence of a diploid stage. Altogether, these analyses provide novel insights into Mamiellales' biogeography and raise novel testable hypotheses about their life cycle and ecology.

Diversity and evolution of bacterial bioluminescence genes in the global ocean.

Although bioluminescent bacteria are the most abundant and widely distributed of all light-emitting organisms, the biological role and evolutionary history of bacterial luminescence are still shrouded in mystery. Bioluminescence has so far been observed in the genomes of three families of Gammaproteobacteria in the form of canonical lux operons that adopt the CDAB(F)E(G) gene order. LuxA and luxB encode the two subunits of bacterial luciferase responsible for light-emission. Our deep exploration of public marine environmental databases considerably expands this view by providing a catalog of new lux homolog sequences, including 401 previously unknown luciferase-related genes. It also reveals a broader diversity of the lux operon organization, which we observed in previously undescribed configurations such as CEDA, CAED and AxxCE. This expanded operon diversity provides clues for deciphering lux operon evolution and propagation within the bacterial domain. Leveraging quantitative tracking of marine bacterial genes afforded by planetary scale metagenomic sampling, our study also reveals that the novel lux genes and operons described herein are more abundant in the global ocean than the canonical CDAB(F)E(G) operon.

The Ocean Gene Atlas: exploring the biogeography of plankton genes online.

The Ocean Gene Atlas is a web service to explore the biogeography of genes from marine planktonic organisms. It allows users to query protein or nucleotide sequences against global ocean reference gene catalogs. With just one click, the abundance and location of target sequences are visualized on world maps as well as their taxonomic distribution. Interactive results panels allow for adjusting cutoffs for alignment quality and displaying the abundances of genes in the context of environmental features (temperature, nutrients, etc.) measured at the time of sampling. The ease of use enables non-bioinformaticians to explore quantitative and contextualized information on genes of interest in the global ocean ecosystem. Currently the Ocean Gene Atlas is deployed with (i) the Ocean Microbial Reference Gene Catalog (OM-RGC) comprising 40 million non-redundant mostly prokaryotic gene sequences associated with both Tara Oceans and Global Ocean Sampling (GOS) gene abundances and (ii) the Marine Atlas of Tara Ocean Unigenes (MATOU) composed of >116 million eukaryote unigenes. Additional datasets will be added upon availability of further marine environmental datasets that provide the required complement of sequence assemblies, raw reads and contextual environmental parameters. Ocean Gene Atlas is a freely-available web service at: http://tara-oceans.mio.osupytheas.fr/ocean-gene-atlas/.

Survey of the green picoalga Bathycoccus genomes in the global ocean.

Bathycoccus is a cosmopolitan green micro-alga belonging to the Mamiellophyceae, a class of picophytoplankton that contains important contributors to oceanic primary production. A single species of Bathycoccus has been described while the existence of two ecotypes has been proposed based on metagenomic data. A genome is available for one strain corresponding to the described phenotype. We report a second genome assembly obtained by a single cell genomics approach corresponding to the second ecotype. The two Bathycoccus genomes are divergent enough to be unambiguously distinguishable in whole DNA metagenomic data although they possess identical sequence of the 18S rRNA gene including in the V9 region. Analysis of 122 global ocean whole DNA metagenome samples from the Tara-Oceans expedition reveals that populations of Bathycoccus that were previously identified by 18S rRNA V9 metabarcodes are only composed of these two genomes. Bathycoccus is relatively abundant and widely distributed in nutrient rich waters. The two genomes rarely co-occur and occupy distinct oceanic niches in particular with respect to depth. Metatranscriptomic data provide evidence for gain or loss of highly expressed genes in some samples, suggesting that the gene repertoire is modulated by environmental conditions.

Ocean plankton. Environmental characteristics of Agulhas rings affect interocean plankton transport.

Agulhas rings provide the principal route for ocean waters to circulate from the Indo-Pacific to the Atlantic basin. Their influence on global ocean circulation is well known, but their role in plankton transport is largely unexplored. We show that, although the coarse taxonomic structure of plankton communities is continuous across the Agulhas choke point, South Atlantic plankton diversity is altered compared with Indian Ocean source populations. Modeling and in situ sampling of a young Agulhas ring indicate that strong vertical mixing drives complex nitrogen cycling, shaping community metabolism and biogeochemical signatures as the ring and associated plankton transit westward. The peculiar local environment inside Agulhas rings may provide a selective mechanism contributing to the limited dispersal of Indian Ocean plankton populations into the Atlantic.