The sex-specific transcriptome of the hermaphrodite sparid sharpsnout seabream (Diplodus puntazzo)

Background: Teleosts are characterized by a remarkable breadth of sexual mechanisms including various forms of hermaphroditism. Sparidae is a fish family exhibiting gonochorism or hermaphroditism even in closely related species. The sparid Diplodus puntazzo (sharpsnout seabream), exhibits rudimentary hermaphroditism characterized by intersexual immature gonads but single-sex mature ones. Apart from the intriguing reproductive biology, it is economically important with a continuously growing aquaculture in the Mediterranean Sea, but limited available genetic resources. Our aim was to characterize the expressed transcriptome of gonads and brains through RNA-Sequencing and explore the properties of genes that exhibit sex-biased expression profiles. Results: Through RNA-Sequencing we obtained an assembled transcriptome of 82,331 loci. The expression analysis uncovered remarkable differences between male and female gonads, while male and female brains were almost identical. Focused search for known targets of sex determination and differentiation in vertebrates built the sex-specific expression profile of sharpsnout seabream. Finally, a thorough genetic marker discovery pipeline led to the retrieval of 85,189 SNPs and 29,076 microsatellites enriching the available genetic markers for this species. Conclusions: We obtained a nearly complete source of transcriptomic sequence as well as marker information for sharpsnout seabream, laying the ground for understanding the complex process of sex differentiation of this economically valuable species. The genes involved include known candidates from other vertebrate species, suggesting a conservation of the toolkit between gonochorists and hermaphrodites

An overview of the reproductive cycle of cultured specimens of a potential candidate for Mediterranean aquaculture, Umbrina cirrosa

The shi drum (Umbrina cirrosa), belonging to the Sciaenidae family of fish (Nelson et al., 2016) has attracted attention as it is an excellent diversification species in Mediterranean aquaculture to combat the low prices of the most cultured species due to the appearance of new producing countries in the Mediterranean area. In this manuscript we describe for the first time the reproductive cycle of captive shi drum specimens that are able to spontaneously spawn in captivity. Our data show that spermatogenesis started in one year old shi drum spe- cimens, although the fish were not mature enough to complete the reproductive cycle. Thus, three year old specimens showed multiple spawns with around 65% of the eggs fertilized. In mature males, levels of 11-ke- totestosterone (11KT), testosterone (T) and progesterone (P) were detected in serum and gonad, while 17β- estradiol (E2) was only detected in gonad. Testicular levels of E2 and P suggest that these hormones might have a role in spawning and in the subsequent spermatogonial proliferation. In mature females, however, P and E2 were detected in serum and gonad, while T and 11KT were only detected in gonad. The pattern shown by P in the ovary indicates a link between this hormone and ovarian renewal and a delay in vitellogenesis, which would explain why the vitellogenic stage of shi drum is quite short. The level of T and 11KT in the ovary suggests a role in oocyte maturation and spawning. The differences observed between sexes in the prevalence of some infection and the important economic losses produced by some vertically transmitted pathogens; have increase the at- tention to the interactions between the immune and reproductive systems. In this study we observed differences between sexes in the protease and bactericide activity levels. Thus, this manuscript represents the most complete overview to date of the shi drum reproductive cycle.Versión del editor2,04

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Plädoyer für eine niedrigschwellige Förderung sozialer Kompetenzen bei Kindern und Jugendlichen

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Temperature-Biased miRNA Expression Patterns during European Sea Bass (Dicentrarchus labrax) Development

Environmental effects and, particularly, temperature changes have been demonstrated to influence the activity, function, and well-being of teleosts. Temperature may change seasonally in the wild, and in captivity under aquaculture operations. Moreover, climate change is expected to shift temperature profiles worldwide. MicroRNAs (miRNA) are important temperature-sensitive gene-expression regulators acting at the post-transcriptional level. They are known to be key regulators in development, reproduction, and immune responses. Therefore, early larval development of the European sea bass (Dicentrarchus labrax), one of the most extensively cultured species in Mediterranean aquaculture, was investigated at early rearing temperatures, i.e., 15, 17.5, and 20 °C, in regard to the impact of temperatures on miRNAs through sncRNA high-throughput sequencing but also at the phenotypic level in terms of growth, sex, vision, and skeletal deformities. Expression profiling revealed stage- and temperature-specific miRNA expression targeting genes with roles in reproduction and immune response mainly at the flexion and all-fins stages. Similar stage- and temperature-specific results were also observed concerning the number of rod cells and lower jaw elongation. The present work presents for the first time highly promising results on the influence of early rearing temperature at the post-transcriptional level during European sea bass development, with a putative impact on reproduction and immune response, as well as regarding teleost vision and larval development

Senescence is a Spi1-induced anti-proliferative mechanism in primary hematopoietic cells

International audienceTranscriptional deregulation caused by epigenetic or genetic alterations is a major cause of leukemic transformation. The Spi1/PU.1 transcription factor is a key regulator of many steps of hematopoiesis, and limits self-renewal of hematopoietic stem cells. The deregulation of its expression or activity contributes to leukemia, in which Spi1 can be either an oncogene or a tumor suppressor. Herein we explored whether cellular senescence, an anti-tumoral pathway that restrains cell proliferation, is a mechanism by which Spi1 limits hematopoietic cell expansion, and thus prevents the development of leukemia. We show that Spi1 overexpression triggers cellular senescence both in primary fibroblasts and hematopoietic cells. Erythroid and myeloid lineages are both prone to Spi1-induced senescence. In hematopoietic cells, Spi1-induced senescence requires its DNA-binding activity and a functional p38MAPK14 pathway but is independent of a DNA-damage response. In contrast, in fibroblasts, Spi1-induced senescence is triggered by a DNA-damage response. Importantly, using our well-established Spi1 transgenic leukemia mouse model, we demonstrate that Spi1 overexpression also induces senescence in erythroid progenitors of the bone marrow in vivo before the onset of the pre-leukemic phase of erythroleukemia. Remarkably, the senescence response is lost during the progression of the disease and erythroid blasts do not display a higher expression of Dec1 and CDKN1A, two of the induced senescence markers in young animals. These results bring indirect evidence that leukemia develops from cells which have bypassed Spi1-induced senescence. Overall, our results reveal senescence as a Spi1-induced anti-proliferative mechanism that may be a safeguard against the development of acute myeloid leukemia

A genetic linkage map of the hermaphrodite teleost fish Sparus aurata L.

The gilthead sea bream (Sparus aurata L.) is a marine fish of great importance for fisheries and aquaculture. It has also a peculiar sex-determination system, being a protandrous hermaphrodite. Here we report the construction of a first-generation genetic linkage map for S. aurata, based on 204 microsatellite markers. Twenty-six linkage groups (LG) were found. The total map length was 1241.9 cM. The ratio between sex-specific map lengths was 1:1.2 (male:female). Comparison with a preliminary radiation hybrid (RH) map reveals a good concordance, as all markers located in a single LG are located in a single RH group, except for Ad-25 and CId-31. Comparison with the Tetraodon nigroviridis genome revealed a considerable number of evolutionary conserved regions (ECRs) between the two species. The mean size of ECRs was 182 bp (sequence identity 60–90%). Forty-one ECRs have a known chromosomal location in the pufferfish genome. Despite the limited number of anchoring points, significant syntenic relationships were found. The linkage map presented here provides a robust comparative framework for QTL analysis in S. aurata and is a step toward the identification of genetic loci involved both in the determination of economically important traits and in the individual timing of sex reversal

Second generation genetic linkage map for the gilthead sea bream Sparus aurata L.

International audienceAn updated second linkage map was constructed for the gilthead sea bream, Sparus aurata L, a fish species of great economic importance for the Mediterranean aquaculture industry. In contrast to the first linkage map which mainly consisted of genomic microsatellites (SSRs), the new linkage map is highly enriched with SSRs found in Expressed Sequence Tags (EST-SSRs), which greatly facilitates comparative mapping with other teleosts. The new map consists of 321 genetic markers in 27 linkage groups (LGs): 232 genomic microsatellites, 85 ESTSSRs and 4 SNPs; of those, 13 markers were linked to LGs but were not ordered. Eleven markers (5 SSRs, 5 EST-SSRs and 1 SNP) are not assigned to any LG. The total length of the sex-averaged map is 1769.7 cM, 42% longer than the previously published one, and the number of markers in each LG ranges from 2 to 30. The inter-marker distance varies from 0 to 75.6 cM, with an average of 5.75 cM. The male and female maps have a length of 1349.2 and 2172.1 cM, respectively, and the average distance between markers is 4.38 and 7.05 cM, respectively. Comparative mapping with the three-spined stickleback (Gasterosteus acuulatus) chromosomes and scaffolds showed conserved synteny with 132 S. aurata markers (42.9% of those mapped) having a hit on the stickleback genome

SRF selectively controls tip cell invasive behavior in angiogenesis

International audienceEfficient angiogenic sprouting is essential for embryonic, postnatal and tumor development. Serum response factor (SRF) is known to be important for embryonic vascular development. Here, we studied the effect of inducible endothelial-specific deletion of Srf in postnatal and adult mice. We find that endothelial SRF activity is vital for postnatal growth and survival, and is equally required for developmental and pathological angiogenesis, including during tumor growth. Our results demonstrate that SRF is selectively required for endothelial filopodia formation and cell contractility during sprouting angiogenesis, but seems dispensable for vascular remodeling. At the molecular level, we observe that vascular endothelial growth factor A induces nuclear accumulation of myocardin-related transcription factors (MRTFs) and regulates MRTF/SRF-dependent target genes including Myl9, which is important for endothelial cell migration in vitro. We conclude that SRF has a unique function in regulating migratory tip cell behavior during sprouting angiogenesis. We hypothesize that targeting the SRF pathway could provide an opportunity to selectively target tip cell filopodia-driven angiogenesis to restrict tumor growth

Single-cell analysis based dissection of clonality in myelofibrosis

Cancer development is an evolutionary genomic process with parallels to Darwinian selection. It requires acquisition of multiple somatic mutations that collectively cause a malignant phenotype and continuous clonal evolution is often linked to tumor progression. Here, we show the clonal evolution structure in 15 myelofibrosis (MF) patients while receiving treatment with JAK inhibitors (mean follow-up 3.9 years). Whole-exome sequencing at multiple time points reveal acquisition of somatic mutations and copy number aberrations over time. While JAK inhibition therapy does not seem to create a clear evolutionary bottleneck, we observe a more complex clonal architecture over time, and appearance of unrelated clones. Disease progression associates with increased genetic heterogeneity and gain of RAS/RTK pathway mutations. Clonal diversity results in clone-specific expansion within different myeloid cell lineages. Single-cell genotyping of circulating CD34 + progenitor cells allows the reconstruction of MF phylogeny demonstrating loss of heterozygosity and parallel evolution as recurrent events