bioRxiv Science⌕ Search

Biology subjects

Kille, P.

Publications and source records attributed to Kille, P..

3 recordsLinked to original sources

Coping with extremes: How Epigenetic and Molecular Adaptations Enable Earthworms to Thrive in Volcanic Soils

Earthworms thriving in naturally occurring geothermal soils offer rare insight into rapid adaptation to environmental extremes. Here, we show that the pantropical earthworm Amynthas gracilis survives and flourishes in soils of the Furnas Volcano (Sao Miguel Island, Azores), where conditions include elevated temperatures (up to 40 {degrees}C), high CO2 (88.6%), low O2 (10%), toxic metals, and mildly acidic pH. In a reciprocal-transplant, mesocosm-based experiment between soils overlying areas of active degassing volcanic gassing (hereafter active degassing soils) and reference soils, convergence of the epidermal thickness of the transplanted earthworms to the resident-soil phenotype (24 {+/-} 3.9 {micro}m active degassing soil, 43.8 {+/-} 8 {micro}m reference soil), was observed within 31 days. Combining RNA-Seq, DNA (5-cytosine) methylation mapping, and microRNA profiling, this phenotypic change results from coordinated transcriptional and epigenetic reprogramming. While gene-body methylation occurred at [~]98 % of loci, levels varied, and differentially methylated regions were enriched ffor genes with altered expression under volcanic stress. Multi-omics network analysis identified epithelial morphogenesis, circulatory system formation, and neural development as regulatory hubs, highlighted by a set of 41 epithelial-morphogenesis genes showing consistent methylation and miRNA patterns. Additional modules governing ion transport and signal transduction complemented the adaptive response. Collectively these findings demonstrate that A. gracilis employs dynamic DNA methylation and microRNA regulation alongside transcriptional reprogramming to generate a persistent phenotypic adjustment to a volcanic stress. This work advances our understanding of extremophile resilience and provides a scalable model for predicting organismal adaptive capacity in the face of environmental extremes.

molecular biology↗

Conserved roles of GATA4 and its target gene TBX2 in regulation of human cardiogenesis

The transcription factor (TF) GATA4 is a key mediator of cardiogenesis. GATA4 regulates cardiogenesis through the expression of its target genes, only some of which have been identified. We have used a gain of function model based on pluripotent embryonic ectoderm explants from Xenopus embryos expressing GATA4, to identify a set of downstream targets of GATA4 which are also regulated by Nodal, a known cardiogenic signal. GATA4 was shown to be required for the expression of target genes tbx2 and prdm1 in vivo, likely acting in a direct fashion by interacting with their regulatory regions. In addition, tbx2 and prdm1 are shown to have roles of their own in vivo, as downregulation of tbx2, a positive target, and overexpression of prdm1, a negative target, interferes with cardiac development in Xenopus embryos. The conservation of the GATA4-TBX2-PRDM1 regulatory relationship was shown in human iPSC-derived cardiomyocytes. Loss of function of GATA4 lead to downregulation of TBX2, upregulation of PRDM1 expression and failure of cardiogenesis. GATA4-deficient cells failed to form normal cardiomyocytes, with most cells adopting alternative fates and only a small minority expressing an aberrant cardiomyocyte phenotype. Genome-wide transcriptomic analysis documented severe reduction of cardiomyocyte and endothelial cell transcriptomes and upregulation of transcriptional profiles of smooth muscle cells and fibroblasts. Disruption of TBX2 function did not alter cardiomyocyte differentiation efficiency but led to the formation of hypertrophic cardiomyocytes characterised by defective sarcomeres and deficient calcium signalling. In addition, we show that whilst PRDM1 is not essential for formation of cardiomyocytes it is implicated in suppression of alternative cell fates. The results presented establish a conserved regulatory relationship between GATA4 and its target genes TBX2 and PRDM1 and roles for these genes in the modulation of cardiomyocyte development, expanding the cardiac gene regulatory network and providing further insight into how cardiogenesis proceeds.

developmental biology↗

Aryl hydrocarbon receptor utilises cellular zinc signals to maintain the gut epithelial barrier

Both zinc and plant-derived ligands of the aryl hydrocarbon receptor (AHR) are dietary components which regulate intestinal epithelial barrier function and protect against Inflammatory Bowel Disease (IBD)1,2. Here, we explore whether zinc and AHR pathway are linked using a mouse IBD model with follow-on studies on human and mouse ileum organoids. Our data demonstrate that AHR regulates cellular zinc uptake, and that zinc is an integral part of AHR signalling processes. We show that dietary supplementation in mice with the plant-derived AHR ligand precursor, indole-3-carbinol (I3C), offers a high level of protection against dextran sulfate sodium induced IBD while protection fails in mice with AHR deleted in the intestinal epithelium. AHR agonist treatment is also ineffective in mice with a nutritional zinc deficiency. Experiments in the human Caco-2 cell line and ileum organoids showed that AHR activation increases total cellular zinc and cytosolic free Zn2+ concentrations through transcriptional upregulation of several SLC39 zinc importers. As a consequence, genes for tight junction (TJ) proteins were upregulated in a zinc-dependent manner involving zinc inhibition of signalling to NF-{kappa}B and attenuated degradation of TJ proteins through zinc inhibition of calpain activity. Thus, our data indicate that AHR activation by plant-derived dietary ligands improves gut barrier function via zinc-dependent cellular pathways, suggesting that combined dietary supplementation with AHR ligands and zinc might be effective in preventing and treating inflammatory gut disorders.

cell biology↗