Biology subjects

Palomer, E.

Publications and source records attributed to Palomer, E..

4 recordsLinked to original sources

bioRxiv2026

EpiFlow: multidimensional single-cell epigenetic profiling by spectral flow cytometry

The epigenetic landscape of individual cells determines their identity and function, yet current methods for profiling chromatin modifications at single-cell resolution remain low-throughput, costly, or limited in parametric depth. Here we present EpiFlow, a spectral flow cytometry-based platform that enables the simultaneous quantification of 16 epigenetic markers, including histone post-translational modifications, DNA methylation, and hydroxymethylation, at the single-cell level. We demonstrate that EpiFlow is robust across species from yeast to mammals and resolves biologically meaningful epigenetic transitions during the cell cycle, stem cell differentiation, germinal centre B cell maturation, diabetic liver remodelling, and seizure-induced chromatin reprogramming. High-dimensional integration of EpiFlow data enables cell-type classification based solely on epigenetic profiles in liver, brain, blood, and cancer. Furthermore, EpiFlow detects on-target and off-target/indirect effects of epigenetic drugs in a high-throughput-compatible format. Collectively, these results establish EpiFlow as a broadly applicable platform for single-cell epigenetic analysis in basic, pharmaceutical, and translational research.

cell biology↗

bioRxiv2026

Embryonic cortical extracellular vesicles confer neuroprotection via multipathway signaling with CaMKIIα as a key mediator

Extracellular vesicles (EVs) are increasingly recognized for their roles in orchestrating embryonic development. Emerging preclinical evidence further suggests that EVs from young organisms possess innate regenerative potential for adult or injured tissues. Here we show that small extracellular vesicles (sEVs) isolated from the mouse embryonic cortex exert neuroprotective effects in vitro and in vivo. Proteomic profiling revealed that embryonic sEVs are enriched with effectors of receptor tyrosine kinase activation, anti-inflammatory responses, and protein synthesis. Notably, we identified BDNF as a surface-bound cargo on embryonic sEVs, displaying superior stability and receptor activation kinetics than its non-vesicular form. Phospho-proteomic analysis further revealed that sEVmediated neuroprotection is driven primarily by the CaMKII signaling axis, which targets downstream effectors of microtubule stability, synaptic plasticity, and membrane-cytoskeleton interactions. Critically, embryonic sEVs, but not those from aged mice, restored microtubule stability and mitochondrial respiration in aged neurons in vitro. Our findings identify embryonic cortical sEVs as significant regulators of neuronal resilience and provide a molecular blueprint for EV-based strategies in neurodegeneration and aging research.

molecular biology↗

bioRxiv2023

LOSS OF CLDN5 -AND INCREASE IN IRF7- IN THE HIPPOCAMPUS AND CEREBRAL CORTEX OF DIABETIC MICE AT THE EARLY SYMPTOMATIC STAGE.

Analyzing changes in gene expression within specific brain regions of individuals with Type 2 Diabetes (T2DM) who do not exhibit significant cognitive deficits can yield valuable insights into the mechanisms that may underlie the progression toward a more severe phenotype, for example as when individuals age. Here, we present evidence that adult mice with long-term type 2 diabetes mellitus (T2DM) and minor cognitive deficits display alterations in the expression of 27 genes in the cerebral cortex and 16 genes in the hippocampus compared to non-T2DM mice. Only six of these genes undergo the same type of change both in the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor {beta}-stimulated clone 22/TSC22 (Tscd3) are all upregulated, while Claudin-5 (Cldn5) is downregulated. At the protein level, Claudin5 and IRF7 showed equivalente changes: downregulation of CLDN5 and upregulation of IRF7. These results suggest that cognitive deficits linked to chronic T2DM may stem from compromised blood-brain barrier integrity and an abnormal inflammatory response in the early stages of the disease. This underscores the potential for therapeutic interventions targeting CLDN5 and IRF7.

neuroscience↗

bioRxiv2021

Epigenetic repression of Wnt receptors in AD: a role for Sirtuin2-induced H4K16ac deacetylation of Frizzled1 and Frizzled7 promoters

Growing evidence supports a role for deficient Wnt signalling in Alzheimer's disease (AD). First, the Wnt antagonist DKK1 is elevated in AD brains and is required for amyloid-{beta}-induced synapse loss. Second, LRP6 Wnt co-receptor is required for synapse integrity and three variants of this receptor are linked to late-onset AD. However, the expression/role of other Wnt signalling components remain poorly explored in AD. Wnt receptors Frizzled1 (Fzd1), Fzd5, Fzd7 and Fzd9 are of interest due to their role in synapse formation/plasticity. Our analyses showed reduced FZD1 and FZD7 mRNA levels in the hippocampus of human early AD stages and in the hAPPNLGF/NLGF mouse model. This transcriptional downregulation was accompanied by reduced levels of the pro-transcriptional histone mark H4K16ac and a concomitant increase of its deacetylase Sirt2 at Fzd1 and Fzd7 promoters in AD. In vitro and in vivo inhibition of Sirt2 rescued Fzd1 and Fzd7 mRNA expression and H4K16ac levels at their promoters. In addition, we showed that Sirt2 recruitment to Fzd1 and Fzd7 promoters is dependent on FoxO1 activity in AD, thus acting as a co-repressor. Finally, we found reduced levels of Sirt2 inhibitory phosphorylation in nuclear samples from human early AD stages with a concomitant increased in the Sirt2 phosphatase PP2C. This results in hyperactive nuclear Sirt2 and favours Fzd1 and Fzd7 repression in AD. Collectively, our findings define a novel role for nuclear hyperactivated Sirt2 in repressing Fzd1 and Fzd7 expression via H4K16ac deacetylation in AD. We propose Sirt2 as an attractive target to ameliorate AD pathology.

neuroscience↗