Biology subjects

Sell, C.

Publications and source records attributed to Sell, C..

4 recordsLinked to original sources

bioRxiv2026

Senescent and reactive astrocytes display distinct expression profiles and divergent functional capacities.

Astrocytes assume multiple phenotypes in the brain in response to stress, injury, inflammation, and aging. Given the complexity of this critical cell type in the CNS, it is important to gain a greater understanding of the differences between these phenotypes and to potentially identify therapeutic approaches to modifying astrocyte function in the context of disease and aging. We compared senescent and reactive astrocytes using a strictly defined paradigm to induce these phenotypes in human astrocytes. Gene expression profiling reveals overlapping but distinct expression profiles. Reactive astrocytes predominantly express genes involved in inflammatory responses while senescent astrocytes express genes and a secretome that suggests a role in synaptic pruning. Unexpectedly, functional analysis in a simplified neurite outgrowth assay suggests that senescent astrocytes retain the ability to support neurite outgrowth while reactive astrocytes lose this capacity. The data suggests that senescent and reactive astrocytes play distinct functional roles in the physiology of the aging brain. However, the overlapping inflammatory nature of senescent and reactive astrocytes makes it difficult to discriminate between them using existing toolsets designed to identify senescent cells.

cell biology↗

bioRxiv2026

Adenosine deaminase co-immunization reverses age-associated immunosenescence by restoring germinal center T follicular helper cell function

Older adults experience disproportionate morbidity and mortality from Clostridioides difficile infection (CDI); however, existing toxoid- and receptor binding domain (RBD)-based vaccines elicit suboptimal protection in aged hosts due to the age-associated defects in CD4+ T cell function, T follicular helper (TFH) cell activation, and antibody quality. We evaluated whether adenosine deaminase (ADA), an enzymatic immune modulator that degrades immunosuppressive adenosine, and improves GC TFH differentiation and survival, could reverse these age-related impairments when co-delivered with DNA vaccine plasmids targeting toxin A and B RBDs (pRBD). In aged mice, pRBD vaccination alone produced markedly reduced toxin-specific effector/memory CD4+ T cells, diminished TFH activation, and poor toxin A neutralization compared to vaccinated young mice. Co-immunization with plasmid-encoded adenosine deaminase-1 (pADA) restored toxin-specific CD4+ T cell generation and cytokine production, activation-induced marker (AIM) TFH responses, and antibody-mediate toxin neutralization to levels comparable to young adults. Mechanistically, pADA co-immunization was associated with the reduction of CXCR4 on germinal center (GC) TFH cells--an age-related defect linked to impaired GC positioning and diminished B cell help--suggesting that ADA improves humoral quality by correcting GC TFH mislocalization. These immune enhancements corresponded with improved clinical outcomes in morbidity, mortality, and weight-loss following C. difficile spore challenge of aged mice. Finally, pADA significantly reduced adenosine levels in aged lymph nodes, implicating a potential enzymatic-based regulation of GC immunosenescence. Together, these findings identify ADA as a metabolic adjuvant capable of reversing key features of vaccine immunosenescence and highlight adenosine dependent CXCR4 regulation as a tractable axis for improving vaccine efficacy in older populations.

immunology↗

bioRxiv2022

lncRNA H19/Let7b/EZH2 axis regulates somatic cell senescence

Long non-coding RNAs (lncRNAs) regulate diverse cellular processes and are associated with many age-associated diseases. However, the function of lncRNAs in cellular senescence remains largely unknown. Here we characterize the role of lncRNA H19 in senescence. We show that H19 levels decline as cells undergo senescence, and depletion of H19 results in premature senescence. We find that repression of H19 is triggered by the loss of CTCF and prolonged activation of p53 as part of the senescence pathway. Mechanistically, the loss of H19 drives senescence via increased let7b mediated targeting of EZH2. We further demonstrate that H19 is required for senescence inhibition by the mTOR inhibitor rapamycin, where it maintains lncRNA H19 levels throughout the cellular lifespan and thus prevents the reduction of EZH2 that would otherwise lead to cellular senescence. Therefore, lncRNA H19 is crucial in maintaining the balance between sustained cell growth and the onset of senescence.

cell biology↗

bioRxiv2017

ATLAS: Analysis Tools for Low-depth and Ancient Samples

SummaryPost-mortem damage (PMD) obstructs the proper analysis of ancient DNA samples and can currently only be addressed by removing or down-weighting potentially damaged data. Here we present ATLAS, a suite of methods to accurately genotype and estimate genetic diversity from ancient samples, while accounting for PMD. It works directly from raw BAM files and enables the building of complete and customized pipelines for the analysis of ancient and other low-depth samples in a very user-friendly way. Based on simulations we show that, in the presence of PMD, a dedicated pipeline of ATLAS calls genotypes more accurately than the state-of-the-art pipeline of GATK combined with mapDamage 2.0.\n\nAvailabilityATLAS is an open-source C++ program freely available at https://bitbucket.org/phaentu/atlas.\n\nContactDaniel.Wegmann@unifr.ch\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗