Biology subjects

Esener, S.

Publications and source records attributed to Esener, S..

5 recordsLinked to original sources

bioRxiv2026

In vivo lineage tracing across human tissues using methylation barcodes in the protocadherin gene cluster

Resolving the lineage history of human cells is fundamental to understanding ageing and cancer but remains hampered by a lack of native, high-resolution markers. Here, we identify the protocadherin (PCDH) gene cluster as a naturally occurring, highly diverse methylation barcode. While PCDH methylation creates neuronal diversity in the brain, we show that stochastic methylation patterns in this region are maintained as heritable, evolvable lineage markers across multiple non-neuronal tissues, including blood, kidney, prostate, and bladder. By tracking these barcodes in serial samples over a decade, we reveal clonal dynamics with high fidelity, quantitatively recapitulating genetic clone sizes. Crucially, PCDH barcodes identify "cryptic" clonal expansions invisible to standard driver-mutation sequencing and resolve subclonal architectures via continuous epimutation. This native barcoding system provides a scalable, driver-agnostic framework for reconstructing somatic evolution in humans.

genomics↗

bioRxiv2025

Lipid Tail Length Determines Nano-Bio Interactions of Peptide Amphiphile Nanostructures

Understanding the interactions of nanomaterials with biological systems is essential to designing effective nanomedicines. However, most of our understanding originates from studies with solid nanoparticles, and nano-bio interactions of self-assembled nanomaterials have remained largely unexplored. To address this knowledge gap, we develop a series of self-assembling peptide amphiphiles (PAs) with different lipid modifications and investigate their interactions with biological systems. We find that PA nanostructures rapidly disassemble and reassemble with albumin and lipoproteins in blood plasma. While PAs with shorter lipid tails mainly assemble with albumin, increasing lipid length shifts binding to lipoproteins. All PAs show strong tumor accumulation in 4T1 tumor-bearing mice with tumor to liver ratios of [~]3-6. Overall, albumin-binding improves blood circulation and tumor accumulation compared to lipoprotein-binding, but also increases off-target accumulation. This study shows that the biointeractions of self-assembled nanomaterials can be controlled through molecular design, which may lead to the development of effective nanomedicines.

bioengineering↗

bioRxiv2025

Methylation dynamics in the decades preceding acute myeloid leukaemia

DNA methylation is emerging as a highly sensitive and specific marker of cancer initiation and progression. How these cancer-specific methylation changes are established in the decades before cancer, however, remains largely unknown. Here, we use a unique collection of longitudinal blood samples collected annually up to 15 years prior to a diagnosis of acute myeloid leukaemia to sensitively track the dynamics of DNA methylation changes at high temporal resolution. We identify thousands of differentially methylated regions (DMRs) that exhibit altered patterns of methylation up to 10 years before acute myeloid leukaemia (AML) diagnosis. Most of these DMRs are strongly associated with expanding clones carrying somatic driver mutations. We identify a subset of epigenetic driver DMRs characterised by recurrent CpG alterations that are highly shared across pre-AML cases. These are likely to reflect early epigenetic reprogramming associated with AML development. We also reveal large numbers of stochastic passenger CpGs whose differential methylation results from hitch-hiking with clonal expansions driven by somatically acquired genetic events. These passenger CpGs can be exploited for lineage tracing to discover clonal expansions driven by missing driver mutations. Our findings show widespread changes in methylation patterns during the early stages of cancer development which could be utilised for risk prediction and therapeutic intervention.

genomics↗

bioRxiv2022

Multiplexed and millimeter-scale superresolution imaging of cells and tissue sections via prism-illumination and microfluidics-enhanced DNA-PAINT

Fluorescence nanoscopy has become increasingly powerful for biomedical research, but it has historically afforded a small field-of-view (FOV) around 50 {micro}m x 50 {micro}m at once and more recently up to ~200 {micro}m x 200 {micro}m. Efforts to further increase the FOV in fluorescence nanoscopy have thus far relied on the use of fabricated waveguide substrates, adding cost and sample constraints on the applications. Here we report PRism-Illumination and Microfluidics-Enhanced DNA-PAINT (PRIME-PAINT) for multiplexed fluorescence nanoscopy across millimeter-scale FOVs. Built upon the well-established prism-type total internal reflection microscopy, PRIME-PAINT achieves robust single-molecule localization with up to ~520 {micro}m x 520 {micro}m single FOVs and 25-40 nm lateral resolutions. Through stitching, nanoscopic imaging over mm2 sample areas can be completed in as little as 40 minutes per target. An on-stage microfluidics chamber facilitates probe exchange for multiplexing and enhances image quality particularly for formalin-fixed paraffin-embedded (FFPE) tissue sections. We demonstrate the utility of PRIME-PAINT by analyzing ~106 caveolae structures in ~1,000 cells and imaging entire pancreatic cancer lesions from patient tissue biopsies. By imaging from nanometers to millimeters with multiplexity and broad sample compatibility, PRIME-PAINT will be useful for building multiscale, Google-Earth-like views of biological systems.

biophysics↗

bioRxiv2020

Electro-optical mechanically flexible coaxial microprobes for minimally invasive interfacing with intrinsic neural circuits

Central to advancing our understanding of neural circuits is the development of minimally invasive, multi-modal interfaces capable of simultaneously recording and modulating neural activity. Recent devices have focused on matching the mechanical compliance of tissue to reduce inflammatory responses1,2. However, reductions in the size of multi-modal interfaces are needed to further improve biocompatibility and long-term recording capabilities1. Here we demonstrate a multi-modal coaxial microprobe design with a minimally invasive footprint (8-12 m diameter over millimeter lengths) that enables efficient electrical and optical interrogation of neural networks. In the brain, the probes allowed robust electrical measurement and optogenetic stimulation. Scalable fabrication strategies can be used with various electrical and optical materials, making the probes highly customizable to experimental requirements, including length, diameter, and mechanical properties. Given their negligible inflammatory response, these probes promise to enable a new generation of readily tunable multi-modal devices for minimally invasive interfacing with neural circuits.

neuroscience↗