FLI Kolloquium with Dr. Christian Nefzger скачать в хорошем качестве

FLI Kolloquium with Dr. Christian Nefzger

Ageing and reprogramming remodel transcription factor networks by hijacking developmental mechanisms In this seminar, Dr. Nefzger explored how cell identity, which is governed by transcription factor (TF) activity, is reshaped during ageing in vivo and reprogramming to pluripotency in vitro by redeploying regulatory logic normally used in development. First, he presented a cross-cell-type atlas of chromatin and transcriptional remodelling during maturation and ageing, revealing a shared TF binding-site signature: early-life enhancers, which are rich in cell-identity TF binding sites, progressively lose accessibility, while AP-1-associated elements open across life and cell types. Their study indicates that AP-1-linked chromatin opening redistributes TF activity away from early-life gene regulatory elements to rewire developmental programmes. This process initially underpins cell maturation programmes and then degrades cell identity in ageing via ongoing AP-1-linked chromatin opening. Second, I Dr. Nefzger introduced DoseH-seq, a dosage-resolved single-nucleus RNA+ATAC assay we developed in the lab to quantify graded TF perturbations. Using a somatic TF whose motifs are enriched in age-closing regions across cell types, he has shown how graded factor overexpression can produce context- and dosage-dependent outcomes: on its own in fibroblasts, it can mitigate mesenchymal drift as a limited form of dedifferentiation or, in synergy with the Yamanaka factors, augment pluripotency induction by re-engaging developmental regulatory elements. The first FLI Colloquium of 2026 was supported by the Aging Research Center of the Friedrich Schiller University. Dr. Christian Nefzger discusses the discovery of an epigenetic mechanism that appears to act as a common driver of aging across multiple mouse tissues. His work identifies a link between pioneering transcription factors and the age-associated opening of chromatin, suggesting that this shift draws essential identity-defining factors away from their canonical binding sites. The resulting erosion of cell identity provides a coherent framework for understanding how epigenetic change contributes to tissue dysfunction during aging. These findings also delineate a conceptual route toward interventions that act on the epigenome to preserve function and extend healthy life. More information: Dr. Christian Nefzger, Institute for Molecular Bioscience, The University of Queensland