Biology subjects

Fernandez-Valverde, S. L.

Publications and source records attributed to Fernandez-Valverde, S. L..

8 recordsLinked to original sources

bioRxiv2025

Gene expression profiling of dendritic cell tolerance dysfunction in women with Systemic lupus erythematosus

Dendritic cells (DCs) are central regulators of immune tolerance, and disturbances in their phenotype and function contribute to the breakdown of self-tolerance in systemic lupus erythematosus (SLE). Tolerogenic DCs (tolDCs), which suppress autoreactive responses and promote peripheral tolerance, are a promising therapeutic focus in autoimmune diseases. Here, we analyzed the transcriptional profiles of in vitro generated DCs derived from monocytes of individuals with SLE and healthy controls to identify disease-specific disruptions in tolerance associated pathways. Interferon stimulated genes (ISGs) emerged as dominant markers across all cellular contexts, with monocytes exhibiting the most substantial enrichment; key ISGs (IFI27, IFI44L, USP18, IFI6) acted as central hubs in regulatory networks, underscoring their diagnostic and pathogenic significance. In tolDCs from SLE donors, lipid metabolism pathways were selectively altered, suggesting impaired synthesis of pro-resolving lipid mediators. Additionally, diminished IL10RA expression and dysregulated IRF4 activity in SLE moDCs indicated intrinsic defects in IL-10 mediated tolerogenic differentiation. Together, these findings suggest that interferon driven transcriptional rewiring, impaired IL-10 signaling, and aberrant lipid metabolic programming converge to compromise DCs tolerogenic capacity in SLE. This highlights key mechanistic pathways that could be targeted to restore immune tolerance and reduce chronic inflammation.

immunology↗

bioRxiv2023

Evolutionary conservation of secondary structures in the lncRNAs of plants

LncRNAs are essential regulators of eukaryotic gene expression. They exert their gene regulatory functions by interacting with DNA, RNA, and protein. These functions are considered at least in part associated with their capacity to fold into complex three-dimensional structures. The conservation of lncRNA structure in mammalian genomes has been assessed in several studies, however, very little is known about the conservation of lncRNA structures in plants. Here, we analyze the structural conservation of lncRNAs in Brassicaceae, using a whole genome alignment of 16 Brassicaceae species. We found that 44.2% (1925 of 4354) of the intergenic lncRNAs (lincRNAs) and 75.1% (1549 of 2060) of the natural antisense transcripts (NATs) of Arabidopsis thaliana have conserved structural motifs in at least 2 of the 16 species. Also, 3612 lncRNAs have conserved structural motifs in multiple species; 2264 of which are tissue-specific, and 841 can be associated with a function by a co-expression network in A. thaliana. Indeed, we find evidence for the conservation of structural motifs in several lncRNAs with known functions, including, lncCOBRA1, FLORE, IPS1, ELENA1 and COOLAIR. The latter was shown previously to have a conserved structure. Overall, we have identified numerous lncRNAs with conserved structures in Brassicaceae that warrant further experimental exploration in vivo to understand whether these lncRNAs and their conserved structures are of biological significance.

bioinformatics↗

bioRxiv2022

Differential RNA-silencing and plasmodesmata callose deposition in leaves and stems of transgenic tobacco plants during Tobacco etch virus infection recovery

Viruses are amongst the most prevalent pathogens that threaten plants. Plants have evolved a sequence-specific defense mechanism against viruses to ensure survival, known as RNA silencing, which includes transcriptional and post-transcriptional gene silencing. After a viral infection, some plants undergo recovery and become further resistant to viral infection. To identify additional mechanisms underlying disease recovery besides the known RNA silencing, we analyzed transgenic tobacco plants expressing a transcript derived from the Nuclear Inclusion "a" protein (NIa) cistron of the tobacco etch virus (TEV), which had recovered from infection three weeks following viral inoculation. Using in situ hybridizations and qRT-PCR, we detected the viral RNA and the transgene-derived transcript in stem sections adjacent to the recovered leaves. To further characterize the silenced and non-silenced conditions, we undertook tissue-specific RNA-Seq and small RNA-Seq analyses in leaf and stem. We found more differentially expressed genes (DEGs) in the recovered leaf, primarily related to defense, silencing, and hormone signaling responses. Finally, we observed differences in plasmodesmata callose deposition and callose-related genes. Overall, our findings suggest that cell-to-cell viral restriction movement also participates in the recovery of TEV infection in transgenic tobacco plants, besides the key function of RNA silencing.

plant biology↗

bioRxiv2022

Nationwide genomic biobank in Mexico unravels demographic history and complex trait architecture from 6,057 individuals

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories as well as complex trait architectures remain hidden due to the lack of Big Data. To fill this gap, the Mexican Biobank project genotyped 1.8 million markers in 6,057 individuals from 32 states and 898 sampling localities across Mexico with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database. Through a suite of state-of-the-art methods for ancestry deconvolution and inference of identity-by-descent (IBD) segments, we inferred detailed ancestral histories for the last 200 generations in different Mesoamerican regions, unraveling native and colonial/post-colonial demographic dynamics. We observed large variations in runs of homozygosity (ROH) among genomic regions with different ancestral origins reflecting their demographic histories, which also affect the distribution of rare deleterious variants across Mexico. We analyzed a range of biomedical complex traits and identified significant genetic and environmental factors explaining their variation, such as ROH found to be significant predictors for trait variation in BMI and triglycerides.

genomics↗

bioRxiv2022

Transcriptome-guided annotation and functional classification of long non-coding RNAs in Arabidopsis thaliana

Long non-coding RNAs (lncRNAs) are a prominent class of eukaryotic regulatory genes. Despite the numerous available transcriptomic datasets, the annotation of plant lncRNAs remains based on dated annotations that have been historically carried over. We present a substantially improved annotation of Arabidopsis thaliana lncRNAs, generated by integrating 224 transcriptomes in multiple tissues, conditions, and developmental stages. We annotate 6764 lncRNA genes, including 3772 that are novel. We characterize their tissue expression patterns and find 1425 lncRNAs are co-expressed with coding genes, with enriched functional categories such as chloroplast organization, photosynthesis, RNA regulation, transcription, and root development. This improved transcription-guided annotation constitutes a valuable resource for studying lncRNAs and the biological processes they may regulate.

genomics↗

bioRxiv2021

Cnidarian hair cell development illuminates an ancient role for the class IV POU transcription factor in defining mechanoreceptor identity

Although specialized mechanosensory cells are found across animal phylogeny, early evolutionary histories of mechanoreceptor development remain enigmatic. Cnidaria (e.g. sea anemones and jellyfishes) is the sister group to well-studied Bilateria (e.g. flies and vertebrates), and has two mechanosensory cell types - a lineage-specific sensory-effector known as the cnidocyte, and a classical mechanosensory neuron referred to as the hair cell. While developmental genetics of cnidocytes is increasingly understood, genes essential for hair cell development are unknown. Here we show that the class IV POU homeodomain transcription factor (POU-IV) - an indispensable regulator of mechanosensory cell differentiation in Bilateria and cnidocyte differentiation in Cnidaria - controls hair cell development in the sea anemone cnidarian Nematostella vectensis. N. vectensis POU-IV is postmitotically expressed in tentacular hair cells, and is necessary for development of the apical mechanosensory apparatus, but not of neurites, in hair cells. Moreover, it binds to deeply conserved DNA recognition elements, and turns on a unique set of effector genes - including the transmembrane-receptor-encoding gene polycystin 1 - specifically in hair cells. Our results suggest that POU-IV directs differentiation of cnidarian hair cells and cnidocytes via distinct gene regulatory mechanisms, and support an evolutionarily ancient role for POU-IV in defining the mature state of mechanosensory neurons.

evolutionary biology↗

bioRxiv2019

Splicing conservation signals in plant long non-coding RNAs

Long non-coding RNAs (lncRNAs) have recently emerged as prominent regulators of gene expression in eukaryotes. LncRNAs often drive the modification and maintenance of gene activation or gene silencing states via chromatin conformation rearrangements. In plants, lncRNAs have been shown to participate in gene regulation, and are essential to processes such as vernalization and photomorphogenesis. Despite their prominent functions only over a dozen lncRNAs have been experimentally and functionally characterized. Similar to its animal counterparts, the rates of sequence divergence are much higher in plant lncRNAs than in protein coding mRNAs, making it difficult to identify lncRNA conservation using traditional sequence comparison methods. Beyond this, little is known about the evolutionary patterns of lncRNAs in plants. Here, we characterized the splicing conservation of lncRNAs in Brassicaceae. We generated a whole-genome alignment of 16 Brassica species and used it to identify synthenic lncRNA orthologues. Using a scoring system trained on transcriptomes from A. thaliana and B. oleracea, we identified splice sites across the whole alignment and measured their conservation. Our analysis revealed that 17.9% (112/627) of all intergenic lncRNAs display splicing conservation in at least one exon, an estimate that is substantially higher to previous estimates of lncRNA conservation in this group. Our findings agree with similar studies in vertebrates, demonstrating that splicing conservation can be evidence of stabilizing selection. We provide conclusive evidence for the existence of evolutionary deeply conserved lncRNAs in plants and describe a generally applicable computational workflow to identify functional lncRNAs in plants.

genomics↗

bioRxiv2018

Diverse RNA interference strategies in early-branching metazoans

BackgroundMicro RNAs (miRNAs) and piwi interacting RNAs (piRNAs), along with the more ancient eukaryotic endogenous small interfering RNAs (endo-siRNAs) constitute the principal components of the RNA interference (RNAi) repertoire of most animals. RNAi in non-bilaterians - sponges, ctenophores, placozoans and cnidarians - appears to be more diverse than that of bilaterians, and includes structurally variable miR-NAs in sponges, an enormous number of piRNAs in cnidarians and the absence of miRNAs in ctenophores and placozoans.\n\nResultsHere we identify thousands of endo-siRNAs and piRNAs from the sponge Amphimedon queens-landica, the ctenophore Mnemiopsis leidyi and the cnidarian Nematostella vectensis using a computational approach that clusters mapped small RNA sequences and annotates each cluster based on the read length and relative abundance of the constituent reads. This approach was validated on 11 small RNA libraries in Drosophila melanogaster, demonstrating the successful annotation of RNAi associated loci with properties consistent with previous reports. In the non-bilaterians we uncover seven new miRNAs from Amphimedon and four from Nematostella as well as sub-populations of candidate cis-natural antisense transcript (cis-NAT) endo-siRNAs. In the ctenophore, the absence of miRNAs is confirmed and an abundance of endo-siRNAs is revealed. Analysis of putative piRNA structure suggests that conserved localised secondary structures in primary transcripts may be important for the production of mature piRNAs in Amphimedon and Nematostella, as is also the case for endo-siRNAs.\n\nConclusionTogether, these findings suggest that the last common ancestor of animals did not have the entrained RNAi system that typifies bilaterians. Instead it appears that bilaterians, cnidarians, ctenophores and sponges express unique repertoires and combinations of miRNAs, piRNAs and endo-siRNAs.

genomics↗