Biology subjects

Honig, F.

Publications and source records attributed to Honig, F..

4 recordsLinked to original sources

bioRxiv2026

Inferring somatic copy number aberrations from spatial transcriptomics data to study early cancer development

Understanding the spatial organisation of cells undergoing early transformation and their interactions with the local microenvironment is critical to studying the earliest stages of cancer development. Somatic copy number aberrations (SCNAs) are among the earliest genomic alterations observed in many cancers, but their spatial context remains difficult to study using conventional sequencing approaches. We developed a computational framework to infer SCNAs directly from Xenium spatial transcriptomics data, enabling the identification and spatial mapping of cell populations sharing common SCNA profiles. Applying this approach to ovarian, cervical and breast cancer datasets identified spatially coherent SCNA-defined populations that recapitulated known tumour-associated copy number aberrations and pathological states. In high-grade serous ovarian cancer, we identified an intermediate epithelial population within the fallopian tube exhibiting features of early transformation accompanied by immune remodelling. Together, our pipeline establishes a scalable framework for reconstructing the spatial architecture of SCNA-defined clones, providing new opportunities to identify and characterise candidate early transforming cell populations in situ.

cancer biology↗

bioRxiv2025

Colorectal cancer progression to metastasis is associated with dynamic genome-wide biphasic 5-hydroxymethylcytosine accumulation.

BackgroundColorectal cancer (CRC) progression from adenoma to adenocarcinoma is associated with global reduction in 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). DNA hypomethylation continues upon liver metastasis. Here we examine 5hmC changes upon progression to liver metastasis. Results5hmC is increased in metastatic liver tissue relative to the primary colon tumour and expression of TET2 and TET3 is negatively correlated with risk for metastasis in patients with CRC. Genes associated with increased 5-hydroxymethylcytosine show KEGG enrichment for adherens junctions, cytoskeleton and cell migration around a core cadherin (CDH2) network. Overall, the 5-hydroxymethylcyosine profile in the liver metastasis is similar to normal colon appearing to recover at many loci where it was originally present in normal colon and then spreading to adjacent sites. The underlying sequences at the recover and spread regions are enriched for SALL4, ZNF770, ZNF121 and PAX5 transcription factor binding sites. Finally, we show in a zebrafish migration assay using SW480 CRISPR-engineered TET knockout and rescue cells that reduced TET expression leads to a reduced migration frequency. ConclusionTogether these results suggest a biphasic trajectory for 5-hydroxymethyation dynamics that has bearing on potential therapeutic interventions aimed at manipulating 5-hydroxymethylcytosine levels.

cancer biology↗

bioRxiv2020

Expanding Biomaterial Surface Topographical Design Space through Natural Surface Reproduction

Surface topography guides cell behavior and is a tool to endow biomaterials with bioactive properties. The large number of possible designs makes it challenging to find the optimal surface structure to induce a specific cell response. The TopoChip platform is currently the largest collection of topographies with 2176 in silico designed micro-topographies. Still, it is exploring only a small part of the design space due to the boundary conditions of the design algorithm and the surface engineering strategy. Inspired by the diversity of natural surfaces, we assessed to what extend we could expand the topographical design space and consequently the resulting cellular responses using natural surfaces. To this end, we replicated twenty-six plant and insect surfaces in polystyrene and quantified their surface properties using white light interferometry, image analysis and principle component analysis. Next, we quantified mesenchymal stem cell morphology and the pattern of Pseudomonas aeruginosa colonization and compared it to previous data from TopoChip screens. Our data show that natural surfaces extended the TopoChip design space. Moreover, the natural surfaces induced MSC morphologies and bacterial attachment patterns not previously observed on the TopoChip. In the future, we will train our design algorithms with the results obtained by natural surface imprint experiments to further explore the design space and bio-active properties of surface topography.

cell biology↗

bioRxiv2020

Surface topography is a context-dependent activator of TGF-β signaling in mesenchymal stem cells

We previously found that surface topographies induce the expression of the Scxa gene, encoding Scleraxis in tenocytes. Because Scxa is a TGF-{beta} responsive gene, we investigated the link between mechanotransduction and TGF-{beta} signaling. We discovered that mesenchymal stem cells exposed to both micro-topographies and TGF-{beta}2 display synergistic induction of SMAD phosphorylation and transcription of the TGF-{beta} target genes SCXA, a-SMA, and SOX9. Pharmacological perturbations revealed that Rho/ROCK/SRF signaling is required for this synergistic response. We further found an activation of the early response genes SRF and EGR1 during the early adaptation phase on micro-topographies, which coincided with higher expression of the TGF-{beta} type-II receptor gene. Of interest, PKC activators Prostratin and Ingenol-3, known for inducing actin reorganization and activation of serum response elements, were able to mimic the topography-induced TGF-{beta} response. These findings provide novel insights into the convergence of mechanobiology and TGF-{beta} signaling, which can lead to improved culture protocols and therapeutic applications.

cell biology↗