Biology subjects

Abdelfattah, A.

Publications and source records attributed to Abdelfattah, A..

6 recordsLinked to original sources

bioRxiv2025

Vascular transcriptional and metabolic changes precede progressive intra-renal microvascular rarefaction in autosomal dominant polycystic kidney disease

BackgroundThe mechanisms contributing to progressive kidney damage in autosomal dominant polycystic kidney disease (ADPKD) remain unclear. Renal microvascular (MV) rarefaction plays an important role in kidney disease, but its natural history, underlying mechanisms, and contributions to renal disease progression in ADPKD remain unknown. We hypothesized that intrarenal MV rarefaction is present early on and is preceded by vascular transcriptional and metabolic changes. MethodsPkd1RC/RC and WT mice (n=16 each) were studied at 1, 6, and 12 months. Total kidney volume (TKV) was measured in vivo (MRI), whereas renal MV architecture (3D-micro-CT), capillary density, perivascular fibrosis, and histomorphometric parameters were assessed ex vivo. In randomly selected Pkd1RC/RC and WT kidneys (n=5, each/timepoint), mRNA-sequencing was performed to identify differentially expressed vasculature-related genes (DEGs). Next, in young individuals with ADPKD and matched controls (n=10 each), plasma cellular energy metabolites were determined (LC-MS/MS), validated in an extended cohort (n=32 and n=16, respectively), and correlated with markers of disease severity and progression. Gene-metabolite interaction networks were generated to integrate DEGs in Pkd1RC/RC at 1 month with metabolites dysregulated in individuals with ADPKD. ResultsRenal MV density was preserved at 1 month but progressively decreased at 6 and 12 months, associated with capillary loss and perivascular fibrosis. A total of 110, 48, and 201 DEGs were identified at 1, 6, and 12 months, respectively. Plasma gamma-aminobutyric acid (GABA) and homocysteine (Hcy) levels were higher in individuals with ADPKD versus controls, interacted with DEGs implicated in inflammatory and innate immune response and Hcy metabolism, and correlated with TKV and renal blood flow. ConclusionsOur data demonstrates that intrarenal MV abnormalities present early in ADPKD and are preceded by vascular transcriptional and metabolic changes. The renal microcirculation may constitute an important therapeutic target in ADPKD, and its underlying biomarkers may serve to monitor its progression. TRANSLATIONAL STATEMENTWe provide the first longitudinal and most comprehensive analysis of the intrarenal microvascular network in a slowly progressive orthologous model of ADPKD and integrate the findings with studies in a young cohort of ADPKD individuals. Our integrated preclinical and clinical data identify vasculature-related pathways that could be targeted for therapeutic interventions and contribute promising, noninvasive biomarkers in patients with ADPKD. Furthermore, because alterations of the intrarenal microcirculation may affect drug delivery, a better understanding of its longitudinal changes may aid in treatment management.

physiology↗

bioRxiv2025

Plant sexual and asexual contributions to the seed microbiome

The seed microbiome plays a key role in the assembly of the plant microbiome, which has major impacts on plant functioning. Nonetheless, little is known about the origin of the seed microbiome. We investigated the relative contributions of two hypothesized transmission routes: sexual inheritance (via reproductive organs) and asexual inheritance (via the plant vascular system). To do that, we sampled shoot endophytes both before bloom and at seed maturity stages, apple flower ovaries and pollen sacs, and mature seeds from field-grown apple trees (Malus domestica BO_SCPLOWORKHC_SCPLOW. cv Gala Galaxy Selecta). We showed that bacterial richness, diversity and composition differ among tissue types, with shoots before bloom harboring a higher diversity than ovary and pollen. Source tracking revealed that both sexual (30.3%) and asexual (23.8%) pathways contributed to seed microbiome assembly, with shoots at seed maturity being the dominant source. Notably, a large proportion (49.5%) of the seed microbiome originated from unknown sources. Lastly, the transmission pathways significantly differed among bacterial genera, with Pseudomonas primarily linked to shoots, Rhizobacter to pollen and Burkholderia to the ovary. Insights into seed microbiome origin offers new opportunities to enhance seed health and crop productivity through microbiome-assisted breeding.

ecology↗

bioRxiv2024

Microcystin shapes the Microcystis phycosphere through community filtering and by influencing cross-feeding interactions

The cyanobacterium Microcystis causes harmful algal blooms (cyanoHABs) that pose a major threat to human health and ecosystem services, particularly due to the prevalence of the potent hepatotoxin microcystin. With their pronounced EPS layer, Microcystis colonies also serve as a hub for heterotrophic phycosphere bacteria. Here, we tested the hypothesis that the genotypic plasticity in its ability to produce microcystin influences the composition and assembly of the Microcystis phycosphere microbiome. In an analysis of individual colonies of a natural Microcystis bloom, we observed a significantly reduced richness of the community in the presence of microcystin biosynthesis genes. A subsequent synthetic community experiment with 21 heterotrophic strains in co-cultivation with either the wild-type strain M. aeruginosa PCC 7806 or the microcystin-free mutant {Delta}mcyB revealed not only a tug-of-war between phototrophic and heterotrophic bacteria, but also a reciprocal dominance of two isolates of the genus Sphingomonas and Flavobacterium. In contrast, an Agrobacterium isolate thrived equally well in both consortia. In substrate utilization tests, Sphingomonas showed the strongest dependence on Microcystis exudates with a clear preference for the wild-type strain. Genome sequencing revealed a high potential for complementary cross-feeding, particularly for the Agrobacterium and Sphingomonas isolates but no potential for microcystin degradation. We postulate that strain-specific functional traits, such as the ability to perform photorespiration and to produce vitamin B12, play a crucial role in the cross-feeding interactions, and that microcystin is one of the determining factors in the Microcystis phycosphere due to its interference with inorganic carbon metabolism.

microbiology↗

bioRxiv2024

Impaired DNA damage response and inflammatory signalling underpins hematopoietic stem cell defects in Gata2 haploinsufficiency

Clinical GATA2 deficiency syndromes arise from germline haploinsufficiency inducing mutations in GATA2, resulting in immunodeficiency that evolves to myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). How GATA2 haploinsufficiency disrupts the function and transcriptional network of hematopoietic stem/progenitors (HSCs/HSPCs) to facilitate the shift from immunodeficiency to pre-leukemia is poorly characterised. Using a conditional mouse model harboring a single allele deletion of Gata2 from the start of HSC development in utero, we identified pervasive defects in HSPC differentiation from young adult Gata2 haploinsufficient mice during B-cell development, early erythroid specification, megakaryocyte maturation to platelets and inflammatory cell generation. Gata2 haploinsufficiency abolished HSC self-renewal and multi-lineage differentiation capacity. These functional alterations closely associated with deregulated DNA damage responses and inflammatory signalling conveyed from Gata2 haploinsufficient HSCs. We identified genetic interplay between Gata2 and Asxl1, a driver of DNA damage and inflammation and, notably, a recurrent secondary mutation found in GATA2 haploinsufficiency disease progression to MDS/AML. shRNA mediated knockdown of Asxl1 in Gata2 haploinsufficient HSPCs led to an enhanced differentiation block in vitro. By analysis of HSCs from young adult compound Gata2/Asxl1 haploinsufficient mice, we discovered hyperproliferation of double haploinsufficient HSCs, which were also functionally compromised in transplantation compared to their single Gata2 or Asxl1 haploinsufficient counterparts. Through both Gata2/Asxl1 dependent and unique transcriptional programs, HSCs from compound Gata2/Asxl1 haploinsufficient fortified deregulated DNA damage responses and inflammatory signalling initiated in Gata2 haploinsufficient HSCs and established a broad pre-leukemic program. Our data reveal how Gata2 haploinsufficiency initially drives deregulation of HSC genome integrity and suggest the mechanisms of how secondary mutations like ASXL1 take advantage of HSC genomic instability to nurture a pre-leukemic state in GATA2 haploinsufficiency syndromes.

cancer biology↗

bioRxiv2022

Plant genotype influence the structure of cereal seed fungal microbiome

Plant genotype is a crucial factor for the assembly of the plant-associated microbial communities. However, we still know little about the variation of diversity and structure of plant microbiomes across host species and genotypes. Here, we used six species of cereals (Avena sativa, Hordeum vulgare, Secale cereale, Triticum aestivum, Triticum polonicum, and Triticum turgidum) to test whether the plant fungal microbiome varies across species, whether plant species use different mechanisms for microbiome assembly focusing on the plant ears. Using ITS2 amplicon sequencing, we found that host species influences the diversity and structure of the seed-associated fungal communities. Then, we tested whether plant genotype influences the structure of seed fungal communities across different cultivars of T. aestivum (Aristato, Bologna, Rosia, and Vernia) and T. turgidum (Capeiti, Cappelli, Mazzancoio, Trinakria, and Timilia). We found that cultivar influences the seed fungal microbiome in both species. We found that in T. aestivum the seed fungal microbiota is more influenced by stochastic processes, while in T. turgidum selection plays a major role. Collectively, our results contribute in filling the knowledge gap on the wheat seed microbiome assembly and might help in understanding how we can manipulate this process to improve agriculture sustainability.

microbiology↗

bioRxiv2018

Impact of Bactrocera oleae on the fungal microbiota of ripe olive drupes.

The olive fruit fly (OFF), Bactrocera oleae is the most devastating pest affecting olive fruit worldwide. Previous investigations have addressed the fungal microbiome associated with olive drupes or B. oleae, but the impact of the insect on fungal communities of olive fruit remains undescribed. In the present work, the fungal microbiome of olive drupes, infested and non-infested by the OFF, was investigated in four different localities and cultivars. Olive fruit fly infestations caused a general reduction of the fungal diversity, a higher quantity of the total DNA and an increase in taxa that remained unidentified or had unknown roles. The infestations led to imbalanced fungal communities with the growth of taxa that are usually outcompeted. While it was difficult to establish a cause-effect link between fly infestation and specific fungi, it is clear that the fly alters the natural microbial balance, especially the low abundant taxa. On the other hand, the most abundant ones, were not significantly influenced by the insect. In fact, despite the slight variation between the sampling locations, Aureobasidium, Cladosporium, and Alternaria, were the dominant genera, suggesting the existence of a typical olive fungal microbiome.

microbiology↗