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Di Palma, F.

Publications and source records attributed to Di Palma, F..

At least 19 recordsLinked to original sources
bioRxiv2026

Intercellular Transfer of PTBP1 Drives Human Neural Stem Cell Fate

During fetal brain development, temporally defined alternative splicing (AS) programs control human neural stem cell (hNSC) self-renewal and differentiation, thereby regulating neurogenesis and gliogenesis. Polypyrimidine tract-binding protein 1 (PTBP1) is a master regulator of AS during neurogenesis; however, its functional role and dynamics in hNSCs remain largely unexplored. Here, we investigate the cellular and molecular functions, nucleocytoplasmic distribution, and intercellular trafficking of PTBP1 in primary hNSCs. We found that PTBP1 knockdown (KD) alters self-renewal capacity, mitochondrial dynamics and membrane potential, lipid droplet abundance, and PTBP2 expression. RNA sequencing analysis revealed that PTBP1 depletion affects the expression profiling of hundreds of coding and non-coding genes, collectively orchestrating a neuronal differentiation program. Super-resolution {tau}-STED microscopy and live-cell imaging demonstrated that PTBP1 localizes not only to the nucleus but also to the cytoplasm, tunneling nanotubes (TNTs), migrasomes, and extracellular vesicles (EVs). Co-culture experiments and EV uptake assays showed that cytosolic PTBP1 can be transferred between hNSCs and delivered to the nuclei of recipient cells via TNTs and EVs. Moreover, EVs were found to contain specific and previously uncharacterized PTBP1 isoforms and were efficiently transferred to PTBP1-KD cells, rescuing their proliferative capacity. Analysis of the mouse brain reveals the presence of PTBP1 in the V-SVZ and within TNT-like structures connecting NSCs, suggesting a role for TNT-mediated PTBP1 trafficking in vivo. Together, these findings uncover previously unrecognized roles for PTBP1 in hNSCs and provide the first evidence that PTBP1 can be transferred between hNSCs via TNTs and EVs, revealing a novel mechanism by which hNSCs may regulate fetal neurogenesis. Graphical AbstractA: PTBP1 regulates hNSC fate by controlling cell proliferation, lipid droplet dynamics, mitochondrial function, and post-transcriptional programs involved in neuronal commitment. B: Cytosolic PTBP1 is transferred between hNSCs via tunneling nanotubes (TNTs) and extracellular vesicles (EVs). Abbreviations: LV, lateral ventricle; aRG, apical radial glial cells; bRG, basal radial glial cells; V-SVZ, ventricular-subventricular zone; EVs, extracellular vesicles; TNTs, tunneling nanotubes.

neuroscience↗
bioRxiv2025

RNA interactions drive structural and functional diversification of alpha-synuclein fibrils

Nucleic acids, particularly RNA, exert multiple roles on protein aggregation, yet their mechanistic involvement remains poorly understood. Building on prior work demonstrating RNA-driven acceleration of protein aggregation, we now demonstrate that RNA binding markedly reshapes the structural and functional properties of alpha-synuclein (aS) fibrils, a protein implicated in Parkinsons disease (PD). Although monomeric aS exhibits negligible RNA-binding properties, aggregation markedly increases its RNA-binding capacity. Our kinetic analyses reveal that RNA incorporation during initial stages of aggregation alters fibril elongation dynamics and modulates surface-mediated secondary nucleation in a seed concentration-dependent manner. Spectroscopic and microscopic characterization (FTIR, micro-FTIR) demonstrate that RNA promotes the formation of structurally distinct, more compact aS fibrils with heterogeneous morphology. Exploiting the recently discovered catalytic hydrolase activity of aS fibrils, we show that direct RNA binding inhibits enzymatic function, consistent with RNA-induced conformational remodeling that limits the exposure of critical residues. Additionally, RNA binding to fibril surfaces impairs proteolytic degradation by proteinase K, suggesting RNA stabilizes fibrils against clearance mechanisms. Moreover, RNA sequencing of fibril-bound nucleic acids uncovers a preference towards uridine-rich motifs that computational docking locates within hydrophilic cavities of disease-associated fibril structures. Collectively, we identify RNA as an active co-factor that remodels structure, propagation kinetics, stability, and function of aS fibrils. We offer a mechanistic link between RNA interaction and amyloid polymorphism relevant to synucleinopathies and, in broader contexts, to amyloid-associated diseases. Significance statementOur work represents the first systematic evidence that RNA directly interacts with protein fibrils and modulates key functional properties such as aggregation kinetics, proteolytic resistance and catalytic activity. We demonstrate that RNA co-aggregates with alpha-synuclein inducing structural conformations that depend on RNA for efficient assembly. Given the resemblance of these RNA-associated fibrils to those found in multiple system atrophy, our findings suggest that the final fibril structures in the patient brain are influenced by multiple cofactors and may differ substantially from recombinant fibrils formed in vitro, even when seeded with patient-derived material.

biochemistry↗
bioRxiv2025

Dissecting Annexin-A11 into its functional domains revealed calcium as a key regulator for RNA transport and its association with ALS

Recent studies reveal a "hitchhiking" mechanism in neurons, where organelles transported along microtubules carry other cargos via tethering molecules. Annexin A11 (ANXA11), a calcium-dependent phospholipid-binding protein, functions as a tether linking RNA granules to lysosomes, aiding mRNA transport for rapid neuronal responses. Structurally, its N-terminal (Nt) binds RNA, while the C-terminal (Ct) associates with lysosomal membranes. Mutations in ANXA11 linked to Amyotrophic lateral sclerosis (ALS) may disrupt this function. Here, applying a multidisciplinary approach, we revealed that Ca2+ acts as a master regulator of ANXAlls physiological function by modulating its conformational states. Specifically, Ca2+ influences a switch between two conformations: a close state, in which the Nt and Ct interact with each other, and an open state, which occurs in the presence of Ca2+ ions, where this self-interaction is disrupted, allowing the two domains to interact freely with RNA and liposomes. Surprisingly, we observed that both the Ct and Nt are capable of interacting with liposomes and RNA in a Ca2+-dependent manner, and these interactions can occur simultaneously. This dual binding and its calcium-regulated hierarchy finely tunes ANXAlls binding to RNA and lysosomes, promoting a large complex essential for overcoming transport steric hindrance. Moreover, our result showed that the p.D40G mutation, in the Nt domain, associated with ALS, displays destabilized interdomain interactions and bypass Ca2+ regulation, leading to aberrant aggregation. These insights advance our understanding of ANXAlls role in neuronal RNA transport and its disruption in neurodegeneration, highlighting potential targets for therapeutic intervention.

biochemistry↗
bioRxiv2025

Computationally-designed aptamers targeting RAD51-BRCA2 interaction inhibit RAD51 nuclear recruitment

The interaction between RAD51 and BRCA2 plays a key role in homologous recombination (HR), a critical DNA repair mechanism essential for the survival of cancer cells. Disrupting this interaction increases the sensitivity of cancer cells to chemotherapeutic agents. Here, we employed in silico methods to design a novel class of aptamers--customized single-stranded oligonucleotides--specifically engineered to bind RAD51. These aptamers were developed with the aim of selectively modulating RAD51s nuclear recruitment and its role in DNA repair processes. The leading candidate displays high affinity for RAD51, competing with BRCA2 for the same interaction site in vitro, as confirmed through biolayer interferometry (BLI) and fluorescence lifetime imaging microscopy (FLIM). We tested the efficacy of the leading aptamer in pancreatic cancer cells and observed that it significantly impedes RAD51 nuclear localization, reduces homologous recombination (HR) efficiency, and increases DNA damage. Critically, our aptamer potentiates the cytotoxicity of the PARP inhibitor olaparib, exploiting synthetic lethality (SL) to induce cancer cell death. Our study showcases an aptamer-based approach for selectively targeting protein interactions within DNA repair pathways, introducing a promising avenue for SL-based treatments applicable to a wide range of cancers.

biochemistry↗
bioRxiv2023

Genome-wide characterisation of pathogenicity-related proteins in Mycena citricolor, the causal agent of the American Leaf Spot in coffee

Mycena citricolor is a fungus that causes the American Leaf Spot (ALS) disease in multiple hosts, including coffee and avocado. This hemibiotroph penetrates the plant through damage induced by oxalic acid. This can cause 20-90% crop losses in coffee depending on the environmental and production conditions. M. citricolor is the only known pathogenic species in the Mycena genus, a large group of saprophytic mushrooms. Comparing the saprophytic and pathogenic genomes can allow us to identify genetic machinery associated with the pathogens genome-wide functional acquisitions to cause disease. To identify pathogenicity-related genes in M. citricolor, we analysed protein family copy-number variation, secretome prediction, and homology to known virulence factors in two M. citricolor assemblies, including a newly assembled and annotated long-read genome. We found that the pathogenic M. citricolor had a higher proportion of secreted genes expanded in copy-number, and expanded gene copies homologous to known virulence factors than the saprophytic Mycena. We shortlisted over 300 candidate genes in each M. citricolor assembly. Focusing on genes strongly regulated during plant interaction, we found over 100 candidates, primarily from multiple copies (up to 4-3 times) of 42 well-known virulence factors (e.g. MFS1, CUTA, NoxA/B, OLE1, NorA), plus a few clade-specific uncharacterised genes. M. citricolor transition to a pathogenic lifestyle reflected genome-wide functional changes. M. citricolor seems to primarily depend on well-known virulence factors in large copy numbers, suggesting the molecular plant-interaction processes involved are like those of better-studied fungi. Hypothetically, the development of ALS resistance could mirror studied responses to these virulence factors.

genomics↗
bioRxiv2023

Characterising genome composition and large structural variation in banana varietal groups

BackgroundBananas and plantains (Musa spp.) are one of the most important crops worldwide. The cultivated varieties are vegetatively propagated, and their diversity is essentially fixed over time. Nevertheless, millennia of diversification and selection have led to hundreds of edible varieties. M. acuminata and M. balbisiana respectively provided the A and B subgenomes that mostly constitute these varieties. Here we aimed to characterise chromosomal exchanges and structural variation among lineages to understand shared foundational events and identify sources of allelic diversity in introgressed loci for genetic improvement. MethodsWe identified clonal somatic groups among 188 banana and plantain accessions introduced for cropping in Colombia, using admixture, principal component, and phylogenetic analyses. We established a new alignment-based metric, named Relative Averaged Alignment (RAA), to infer subgenome composition (AA, AAB, etc.). We later used comparisons in read coverage along conserved chromosomal windows between the A, B, and S subgenomes to identify introgressions. ResultsIn our panel, we identify ten varietal groups composed of somatic clones, plus three groups of tetraploid accessions. We demonstrated RAA can be used to infer subgenome composition in the total genome and individual chromosomes. We identified 20 introgressions, several newly reported, among the AAB and ABB varieties. We did not observe B-donor introgression in any AA/AAA varietal groups. We identified variation in length in at least two introgressions, a B-donor introgression in chromosome 7 between the "Maoli" and a "Popoulu" subdivisions, and an S-donor (M. schizocarpa) introgression in chromosome 2 in four varietal groups with different compositions (AAA, AAB, ABB, and AA). ConclusionsThe extensive distribution of introgressions and the variation in the length of some introgressions between varieties support that the emergence of many varieties can be attributed to intricate founding events, which encompassed multiple instances of hybridisation and subsequent residual backcrossing. We also showed the contribution of M. schizocarpa to four cultivated varieties, and proposed subdivision-specific intergenomic recombination in chromosome 7 between subgroups Maoli and Popoulu plantains. Introgressed loci over these 20 introgressions likely provide an extensive resource of allelic diversity to further explore their contribution to disease resistance, climatic adaption, etc. and potential for exploiting in breeding and genome editing.

plant biology↗
bioRxiv2023

Ancient and ongoing hybridization in the Oreochromis cichlid fishes

Hybridization may enable adaptive diversification by generating unique genetic combinations when hybrid lineages are faced with ecological opportunity. Conversely, hybridization with exotic species may be detrimental to native biodiversity, by leading to homogenisation and the loss of important genetic material associated with local adaptation. Here we studied both ancient and contemporary hybridization in cichlid fishes of the genus Oreochromis (tilapia), which are among the most important fish for global aquaculture. We use whole genome resequencing of 575 individuals from 23 species, focussing on Tanzania, a natural hotspot of tilapia diversity, and a country where hybridization between exotic and native species in the natural environment has been previously reported. We reconstruct the first genome-scale phylogeny of the genus and reveal prevalent ancient gene flow across the Oreochromis phylogeny. This introgression has not led to large-scale adaptive radiation as seen in other cichlid lineages. We identify multiple cases of contemporary hybridization between native and introduced species in the wild, linked to the use of non-native species in aquaculture improvement and stocking for capture fisheries. Our study shows how ancient hybridization contributed to modern tilapia diversity, but is now a threat to both the genetic integrity of wild populations and the long-term prospects of the global tilapia aquaculture industry.

evolutionary biology↗
bioRxiv2023

Chromatin accessibility associated with aquaculture relevant traits in tilapia

The Nile tilapia (Oreochromis niloticus) accounts for [~]9% of global freshwater finfish production however, extreme cold weather and decreasing freshwater resources has created the need to develop resilient strains. By determining the genetic bases of aquaculture relevant traits, we can genotype and breed desirable traits into farmed strains. We developed and optimised ATAC-seq from O. niloticus gill tissues to identify regulatory regions accounting for gene expression associated with gill adaptations. We find that SNPs from 27 tilapia species are enriched in noncoding regions, with 95% of accessible gene promoter regions being SNP-containing. Regulatory variants of TF binding sites are likely driving gene expression differences associated with tilapia gill adaptations, and differentially segregate in freshwater and euryhaline tilapia species. The generation of novel open chromatin data integrated with gene expression and genetic variants revealed candidate genes, genetic relationships, and loci associated with aquaculture relevant traits like salinity and osmotic stress acclimation.

genomics↗
bioRxiv2021

Extensive genome introgression between domestic ferret and European polecat during population recovery in Great Britain.

The European polecat (Mustela putorius) is a mammalian predator which occurs across much of Europe east to the Ural Mountains. In Great Britain, following years of persecution the European polecat has recently undergone a population increase due to legal protection and its range now overlaps that of feral domestic ferrets (Mustela putorius furo). During this range expansion, European polecats hybridised with feral domestic ferrets producing viable offspring. Here we carry out population-level whole genome sequencing on domestic ferrets, British European polecats, and European polecats from the European mainland and find high degrees of genome introgression in British polecats outside their previous stronghold, even in those individuals phenotyped as pure polecats. We quantify this introgression and find introgressed genes under selection that may assist in cognitive function and sight.

evolutionary biology↗
bioRxiv2021

Evolution of miRNA binding sites and regulatory networks in cichlids

The divergence of regulatory regions and gene regulatory network (GRN) rewiring is a key driver of cichlid phenotypic diversity. However, the contribution of miRNA binding site turnover has yet to be linked to GRN evolution across cichlids. Here, we extend our previous studies by analysing the selective constraints driving evolution of miRNA and transcription factor (TF) binding sites of target genes, to infer instances of cichlid GRN rewiring associated with regulatory binding site turnover. Comparative analyses identified increased species-specific networks that are functionally associated to traits of cichlid phenotypic diversity. The evolutionary rewiring is associated with differential models of miRNA and TF binding site turnover, driven by a high proportion of fast-evolving polymorphic sites in adaptive trait genes compared to subsets of random genes. Positive selection acting upon discrete mutations in these regulatory regions is likely to be an important mechanism in rewiring GRNs in rapidly radiating cichlids. Regulatory variants of functionally associated miRNA and TF binding sites of visual opsin genes differentially segregate according to phylogeny and ecology of Lake Malawi species, identifying both rewired e.g. clade-specific and conserved network motifs of adaptive trait associated GRNs. Our approach revealed several novel candidate regulators, regulatory regions and three-node motifs across cichlid genomes with previously reported associations to known adaptive evolutionary traits.

molecular biology↗
bioRxiv2021

Probing interplays between human XBP1u translational arrest peptide and 80S ribosome

The ribosome stalling mechanism is a crucial biological process; yet its atomistic underpinning is still elusive. In this framework, the XBP1u translational arrest peptide (AP) plays a central role in regulating the Unfolded Protein Response (UPR) in eukaryotic cells. Here, we report multi-microseconds all atom molecular dynamics simulations designed to probe the interactions between the XBP1u AP and the mammalian ribosome exit tunnel, both for the wild type AP and for four mutant variants of different arrest potency. Enhanced sampling simulations allow investigating the AP release process of the different variants shedding light on this complex mechanism. The present outcomes are in qualitative/quantitative agreement with available experimental data. In conclusion, we provide an unprecedented atomistic picture of this biological process and clear-cut insights into the key AP-ribosome interactions.

molecular biology↗
bioRxiv2020

Predicting future from past: The genomic basis of recurrent and rapid stickleback evolution

Similar forms often evolve repeatedly in nature, raising longstanding questions about the underlying mechanisms. Here we use repeated evolution in sticklebacks to identify a large set of genomic loci that change recurrently during colonization of new freshwater habitats by marine fish. The same loci used repeatedly in extant populations also show rapid allele frequency changes when new freshwater populations are experimentally established from marine ancestors. Dramatic genotypic and phenotypic changes arise within 5-7 years, facilitated by standing genetic variation and linkage between adaptive regions. Both the speed and location of changes can be predicted using empirical observations of recurrence in natural populations or fundamental genomic features like allelic age, recombination rates, density of divergent loci, and overlap with mapped traits. A composite model trained on these stickleback features can also predict the location of key evolutionary loci in Darwins finches, suggesting similar features are important for evolution across diverse taxa.

evolutionary biology↗
bioRxiv2020

Newly discovered tilapia cichlid fish biodiversity threatened by hybridization with non-native species

Invasive freshwater fish systems are known to readily hybridize with indigenous congeneric species, driving loss of unique and irreplaceable genetic resources. Here we reveal that newly discovered (2013-2016) evolutionarily significant populations of Korogwe tilapia (Oreochromis korogwe) from southern Tanzania are threatened by hybridization with the larger invasive Nile tilapia (Oreochromis niloticus). We use a combination of morphology, microsatellite allele frequencies and whole genome sequences to show that O. korogwe from southern lakes (Nambawala, Rutamba and Mitupa) are distinct from geographically-disjunct populations in northern Tanzania (Zigi River and Mlingano Dam). We also provide genetic evidence of O. korogwe x niloticus hybrids in three lakes and demonstrate heterogeneity in the extent of admixture across the genome. Finally, using the least admixed genomic regions we estimate that the northern and southern O. korogwe populations most plausibly diverged approximately 140,000 years ago, suggesting that the geographical separation of the northern and southern groups is not a result of a recent translocation, and instead these populations represent independent evolutionarily significant units. We conclude that these newly-discovered and phenotypically unique cichlid populations are already threatened by hybridization with an invasive species, and propose that these irreplaceable genetic resources would benefit from conservation interventions.

zoology↗
bioRxiv2019

microRNA profiling in the Weddell Seal suggests novel regulatory mechanisms contributing to diving adaptation

The Weddell Seal (Leptonychotes weddelli) represents a remarkable example of adaptation to diving among marine mammals. This species is capable of diving >900 m deep and remaining underwater for more than 60 minutes. A number of key physiological specializations have been identified, including the low levels of aerobic, lipid-based metabolism under hypoxia, significant increase in oxygen storage in blood and muscle; high blood volume and extreme cardiovascular control. These adaptations have been linked to increased abundance of key proteins, suggesting an important, yet still understudied role for gene reprogramming. In this study, we investigate the possibility that post-transcriptional gene regulation by microRNAs (miRNAs) has contributed to the adaptive evolution of diving capacities in the Weddell Seal. Using small RNA data across 4 tissues (cortex, heart, muscle and plasma), in 3 biological replicates, we generate the first miRNA annotation in this species, consisting of 559 high confidence, manually curated miRNA loci. Evolutionary analyses of miRNA gain and loss highlight a high number of Weddell seal specific miRNAs. 416 miRNAs were differentially expressed (DE) among tissues, whereas 83 miRNAs were differentially expressed (DE) across all tissues between pups and adults and 221 miRNAs demonstrated developmental changes in specific tissues only. mRNA targets of these altered miRNAs identify possible protective mechanisms in individual tissues, particularly relevant to hypoxia tolerance, anti-apoptotic pathways, and nitric oxide signal transduction. Novel, lineage-specific miRNAs associated with developmental changes target genes with roles in angiogenesis and vasoregulatory signaling. Altogether, we provide an overview of miRNA composition and evolution in the Weddell seal, and the first insights into their possible role in the specialization to diving.

evolutionary biology↗
bioRxiv2019

A new Brachiaria reference genome and its application in identifying genes associated with natural variation in tolerance to acidic soil conditions among Brachiaria grasses

Toxic concentrations of aluminium cations and low phosphorus availability are the main yield-limiting factors in acidic soils, which represent half of the potentially available arable land. Brachiaria grasses, which are commonly sown as a forage in the tropics because of their resilience and low demand for nutrients, have a greater tolerance to high concentrations of aluminium cations than most other grass crops. In this work, we explored the natural variation in tolerance to aluminium cations (Al3+) between high and low tolerant Brachiaria species and characterised their transcriptional differences during stress. We also identified three QTLs associated with root vigour during Al3+ stress in their hybrid progeny. By integrating these results with a new Brachiaria reference genome, we have identified 30 genes responsible for Al3+ tolerance in Brachiaria. We also observed differential expression during stress of genes involved in RNA translation, response signalling, cell wall composition and vesicle location genes homologous to aluminium-induced proteins involved in limiting uptake or localizing the toxin. However, there was limited regulation of malate transporters in Brachiaria, which are associated with external tolerance mechanisms to Al3+ stress in other grasses. The contrasting regulation of RNA translation and response signalling suggests response phasing is critical to Al3+ tolerance. HIGHLIGHTWe identified QTLs, genes and molecular responses in high and low tolerant Brachiaria grasses associated with aspects of response to aluminium stress, such as regulation, cell-wall composition and active transport.

genomics↗
bioRxiv2019

Sequencing smart: De novo sequencing and assembly approaches for non-model mammals.

BackgroundWhilst much sequencing effort has focused on key mammalian model organisms such as mouse and human, little is known about the correlation between genome sequencing techniques for non-model mammals and genome assembly quality. This is especially relevant to non-model mammals, where the samples to be sequenced are often degraded and low quality. A key aspect when planning a genome project is the choice of sequencing data to generate. This decision is driven by several factors, including the biological questions being asked, the quality of DNA available, and the availability of funds. Cutting-edge sequencing technologies now make it possible to achieve highly contiguous, chromosome-level genome assemblies, but relies on good quality high-molecular-weight DNA. The funds to generate and combining these data are often only available within large consortiums and sequencing initiatives, and are often not affordable for many independent research groups. For many researchers, value-for-money is a key factor when considering the generation of genomic sequencing data. Here we use a range of different genomic technologies generated from a roadkill European Polecat (Mustela putorius) to assess various assembly techniques on this low-quality sample. We evaluated different approaches for de novo assemblies and discuss their value in relation to biological analyses.\n\nResultsGenerally, assemblies containing more data types achieved better scores in our ranking system. However, when accounting for misassemblies, this was not always the case for Bionano and low-coverage 10x Genomics (for scaffolding only). We also find that the extra cost associated with combining multiple data types is not necessarily associated with better genome assemblies.\n\nConclusionsThe high degree of variability between each de novo assembly method (assessed from the seven key metrics) highlights the importance of carefully devising the sequencing strategy to be able to carry out the desired analysis. Adding more data to genome assemblies not always results in better assemblies so it is important to understand the nuances of genomic data integration explained here, in order to obtain cost-effective value-for-money when sequencing genomes.

genomics↗
bioRxiv2019

Identification of master regulators in goblet cells and Paneth cells using transcriptomics profiling of gut organoids and multi-layered networks

The epithelial lining of the small intestine consists of multiple cell types, including Paneth cells and goblet cells, that work in cohort to maintain gut health. 3D in vitro cultures of human primary epithelial cells, called organoids, have become a key model to study the functions of Paneth cells and goblet cells in normal and diseased conditions. Advances in these models include the ability to skew differentiation to particular lineages, providing a useful tool to study cell type specific function/dysfunction in the context of the epithelium. Here, we use comprehensive profiling of mRNA, microRNA and long non-coding RNA expression to confirm that Paneth cell and goblet cell enrichment of murine small intestinal organoids (enteroids) establishes a physiologically accurate model. We employ network analysis to infer the regulatory landscape altered by skewing differentiation, and using knowledge of cell type specific markers, we predict key regulators of cell type specific functions: Cebpa, Jun, Nr1d1 and Rxra specific to Paneth cells, Gfi1b and Myc specific for goblet cells and Ets1, Nr3c1 and Vdr shared between them. Links identified between these regulators and cellular phenotypes of inflammatory bowel disease (IBD) suggest that global regulatory rewiring during or after differentiation of Paneth cells and goblet cells could contribute to IBD aetiology. Future application of cell type enriched enteroids combined with the presented computational workflow can be used to disentangle multifactorial mechanisms of these cell types and propose regulators whose pharmacological targeting could be advantageous in treating IBD patients with Crohns disease or ulcerative colitis.\n\nTable of contentsWe demonstrate the application of network biology techniques to increase understanding of intestinal dysbiosis through studying transcriptomics data from Paneth and goblet cell enriched enteroids.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC=\"FIGDIR/small/575845v4_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (25K):\norg.highwire.dtl.DTLVardef@16637e5org.highwire.dtl.DTLVardef@1dfaa77org.highwire.dtl.DTLVardef@1307c00org.highwire.dtl.DTLVardef@1d16e0_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗