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Hersch-Gonzalez, J.

Publications and source records attributed to Hersch-Gonzalez, J..

2 recordsLinked to original sources

Phenotypic and transcriptomic similarity between the N2 Ancestral and a Tropical wild isolate of C. elegans reveals divergence from the reference Bristol strain

In recent years, the scientific community has increasingly recognized the importance of incorporating ecologically relevant perspectives into laboratory research. In the case of the free-living nematode Caenorhabditis elegans, numerous studies have documented the domestication of the N2 Bristol strain (isolated in 1951). This has led to a growing interest in recently isolated wild strains from diverse latitudes, which offer insights into natural variation evolution and life-history traits. Here, we compared a recently isolated tropical strain from Mexico City to the N2 Bristol strain. To contextualize laboratory adaptation, we also included the N2 Ancestral strain, a cryopreserved lineage from 1969 with minimal generational drift. Phenotypic assays revealed that, under standard laboratory conditions, the Mexican strain exhibited reduced lifespan and fertility, but enhanced resistance to Pseudomonas aeruginosa, whereas the Ancestral strain showed higher oxidative stress tolerance but reduced thermotolerance. RNA-seq analyses showed that transcriptomic profiles of the Mexican and Ancestral strains were more similar to each other than to the N2 Bristol, suggesting that long-term domestication has driven regulatory divergence. Differential gene expression analyses identified strain-specific signatures in stress, immune and collagen-related pathways. Under heat stress, transcriptional profiling revealed that only a small set of canonical heat shock genes was commonly upregulated across the three strains, yet wild strains showed more dynamic regulation, while N2 Bristol exhibited a distinct, possible preconditioned response. These findings reveal phenotypic trade-offs and regulatory divergence shaped by natural versus laboratory environments, and underscore evolutionary dynamics and adaptive potential of C. elegans in response to distinct ecological histories.

evolutionary biology↗

NRF2 pathway activation reverts high-glucose-induced transcriptional memory in endothelial cells

Various diabetes complications, including nephropathy, retinopathy, and cardiovascular disease, arise from vascular dysfunction. In this context, it has been observed that past hyperglycaemic events can induce long-lasting transcriptional changes, a phenomenon termed "metabolic memory". Yet, the underlying mechanisms driving these persistent effects are not fully characterized. In this study, we evaluated the genome-wide gene expression and chromatin accessibility alterations caused by transient high glucose exposure in human endothelial cells (ECs). We found that cells exposed to a transient high glucose episode had decreased glycolytic and oxygen consumption rates. Transcriptional profiling indicated that high glucose exposure induced substantial changes in the expression of genes belonging to pathways known to be impaired in diabetes, such as TGF-beta, TNF, FoxO, p53, and NRF2 pathways, many of which were retained after normalization of glucose concentrations. Furthermore, analysis of chromatin accessibility showed that transient hyperglycaemia can induce persistent modifications in the accessibility landscape, with the majority of differentially accessible regions located in non-promoter regions. Some of these regions were identified as putative enhancers with neighbouring genes persistently altered after transient high glucose exposure. Finally, we showed that activation of the NRF2 pathway through either NRF2 overexpression or supplementation with the plant-derived compound sulforaphane, was able to substantially revert the glucose-induced transcriptional memory in ECs. Our findings demonstrate that transient high glucose can induce persistent changes in both the transcriptomic and chromatin accessibility profiles of ECs, and that pharmacological NRF2 pathway activation is able to prevent and revert the high-glucose-induced transcriptional memory. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC="FIGDIR/small/557207v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@b9c938org.highwire.dtl.DTLVardef@1498a43org.highwire.dtl.DTLVardef@1146ab5org.highwire.dtl.DTLVardef@169bfca_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗