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37 Publications visible to you, out of a total of 37
Transcriptomic profiling identifies immunotherapy-responsive phenotypes in microsatellite-stable metastatic colorectal cancer.

Abstract (Expand)

Conventional immune checkpoint inhibitors (ICIs) remain largely ineffective in microsatellite-stable metastatic colorectal cancer (MSS mCRC), where low tumor immunogenicity and molecular heterogeneity … across metastatic sites underpin therapeutic resistance. We present a comprehensive transcriptomics analysis of metastatic and primary tumor biopsies from MSS mCRC patients treated with botensilimab (BOT; Fc-enhanced anti-CTLA-4) +/- balstilimab (BAL; anti-PD-1). Self-organizing map (SOM) machine learning stratified tumors into four molecular types, including a liver-like (LIV) subtype characterized by metabolic reprogramming and immunosuppressive signatures, and proliferative (PRO), inflammatory (INF), and mesenchymal (MES) types concordant with pan-cancer classifications. PRO, INF, and MES types were enriched for epithelial tumor cells, immune cells, and fibroblasts, respectively, defining immune-depleted, immune-enriched, and fibrotic states along a plasticity gradient. We observed treatment-related transcriptomic shifts toward immune-enriched states via upregulation of antigen presentation, T cell recruitment, and cytotoxicity pathways. INF and MES tumor types exhibited improved clinical responses and survival vs PRO and LIV types. This study identified distinct tumor microenvironment states that align along an immunophenotype axis marked by CD74, interferon-gamma, and APOBEC3 expression identified previously for primary CRC. Our findings provide novel insights into molecular correlates of immunotherapy response in MSS mCRC, potentially informing future therapeutic strategies to expand ICI efficacy to historically unresponsive tumors.

Authors: T. Konecny, N. Zadirako, A. Grigoryan, M. Tamazyan, S. Mnatsakanyan, L. Stepanyan, H. Loeffler-Wirth, S. Bourdelais, G. Mednick, C. Delepine, D. Chand, H. Binder

Date Published: 16th Jun 2026

Publication Type: Journal

Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma.

Abstract (Expand)

Lymph node (LN) function requires the organization of cells into higher-order spatial units. However, the principles governing LN architecture in health and disease remain poorly understood. Here, we … used single-cell and spatial mapping to investigate the mechanisms directing immune cell organization in human LNs and its disruption in architecturally distinct lymphoma entities: indolent follicular lymphoma (FL) and aggressive diffuse large B cell lymphoma (DLBCL). Our data substantiate the central role of LN-resident stromal cells in chemokine-driven lymphocyte zonation and reveal an inflammatory feedback loop fueled by tumor-reactive T cells that triggers stromal remodeling, progressive loss of homeostatic chemokine gradients, and tissue disorganization from a non-malignant state to FL and DLBCL. Loss of homeostatic chemokines was associated with adverse patient survival, identifying the underlying architectural rearrangement as a key event during lymphomagenesis. Collectively, our results highlight the principles of LN organization and suggest how lymphoma-induced microenvironmental reprogramming drives the loss of tissue organization.

Authors: F. Czernilofsky, A. Mathioudaki, L. Jopp-Saile, R. Lutz, D. Vonficht, X. Wang, C. Schniederjohann, H. Voehringer, T. Roider, M. A. Baertsch, C. Rodemer, H. Loffler-Wirth, M. Grau, D. Fitzgerald, J. Mammen, J. Kosla, N. Liebers, P. M. Bruch, D. Ordonez-Rueda, A. Brobeil, G. Mechtersheimer, C. Pabst, C. Muller-Tidow, A. Trumpp, M. Seifert, F. Neumann, M. Heikenwalder, V. Benes, W. Huber, J. Distler, G. Lenz, H. Binder, R. Siebert, G. P. Nolan, M. Gerstung, J. B. Zaugg, D. Hubschmann, S. Haas, S. Dietrich

Date Published: 31st Mar 2026

Publication Type: Journal

Spotting a unicorn: spatial transcriptome analysis of the eyelid reveals gene regulatory networks enriched in Moll glands.

Abstract (Expand)

Moll glands, found in the margin of the eyelid next to the base of the eyelashes, are likely to play an important role in maintaining the tear film and therefore in securing adequate visual function. … However, information about their secretion and its regulation is extremely scarce. Here, we subjected spatial transcriptome data of the human eyelid to bioinformatics workflows incorporating machine learning to shed light on the Moll-specific transcriptional program. We identified Moll-specific genes such as HPD, CYP4Z1, PIP, GLYATL2, or SCGB2A2, which delineate a transcriptional core, i.e. not shared with other eyelid elements. Gene ontology enrichment analyses further depicted the biological functions of the Moll gland transcriptional programs, which include tyrosine metabolism and biosynthesis, extracellular exosome, small molecule metabolism, and erythrose 4-phosphate/phosphoenolpyruvate-family amino acid metabolism. Expression of GLYATL2 and HPD, identified as a specific and sensitive transcripts in the Moll gland transcriptome, was confirmed by immunofluorescence in the eyelid of four different patients, thus supporting the validity of our approach. Collectively, these results indicate that Moll-associated gene sets exhibit distinct but complementary functional programs, reflecting the gland's specialized metabolic capacity and secretory function within the eyelid tissue microenvironment. Our study provides the first in-depth analysis of the human Moll gland transcriptional landscape and identifies novel targets for regulating Moll gland homeostasis in health and disease.

Authors: T. Konecny, H. Binder, U. Hampel, F. Hansmann, H. Pfannkuche, M. R. Schneider

Date Published: 1st Mar 2026

Publication Type: Journal

Population structure of wild and cultivated grapevines in Armenia

Abstract (Expand)

Background: The South Caucasus region, including Armenia, is recognized as a center of early viticulture, home to the oldest known winery and a rich tradition of winemaking. Armenia's topography … has contributed to the preservation of genetically diverse grapevine populations. Cultivated grapevines (Vitis vinifera ssp. vinifera or V.V. ssp. vinifera) and their wild ancestor (V. vinifera ssp. sylvestris or V.V. ssp. sylvestris) exhibit high genetic diversity, making them valuable resources for understanding domestication, adaptation, and breeding. Despite Armenia’s historical and economic importance, the genomic diversity of its wild and cultivated grapevines remains underexplored. We re-analyzed whole-genome sequencing data of 164 grapevine accessions from Armenia, including cultivated and wild individuals, taken from a previous study on worldwide collected vine accessions to characterize genomic diversity, population structure, and domestication history of this gene pool. Results: Our analysis uncovered genetic patterns partly unique to Armenia. Population structure analysis revealed a clear genetic separation between wild and cultivated groups and three distinct ancestral components within the cultivated gene pool, reflecting a west-to-east geographical gradient in Armenia. This genetic cline correlates with a shift in usage, from table to wine grapes, and a transition in berry skin color from white to black. Additionally, we identified four distinct subgroups within wild populations in Syunik, suggesting notable diversity. Evolutionary history analysis indicates that wild and cultivated lineages began to separate ~18.5k years ago, with divergence intensifying ~4k years ago under human cultivation. Comparative genomic scans for divergent selection identified genomic regions associated with domestication traits, including disease resistance and biosynthesis of anthocyanin and flavanol. Genome-wide association, including k-mer-based approach studies, uncovered candidate markers linked to agronomic traits, such as berry skin color and bunch density. These results provide genomic resources and highlight targets for grapevine improvement and conservation. Conclusions: This whole-genome study on the genetic diversity of wild and cultivated grapevines from Armenia provides a valuable resource for identifying candidate genes and domestication-related regions associated with agronomic traits. The results underscore the importance of conserving local grapevine diversity in Armenia, a historically significant and genetically rich viticultural region.

Authors: Maria Nikoghosyan, Emma Hovhannisyan, Nate Zadirako, Shengchang Duan, Armine Asatryan, Arsen Arakelyan, Kristine Margaryan, Anush Baloyan, Tomas Konecny, Hans Binder

Date Published: 11th Feb 2026

Publication Type: Journal

Annual transcriptomic trajectory of grapevine buds reveals the coordinated regulation of thiamine and stilbenoid biosynthesis during winter dormancy.

Abstract (Expand)

Bud dormancy is a critical survival strategy for perennial plants in temperate climates to endure winter, involving complex transcriptional reprogramming. While previous studies have investigated gene … expression during discrete phases of the grapevine bud annual cycle, a holistic understanding requires an integrated, season-wide analysis. We conducted a meta-analysis by combining and reexamining the transcriptomic data from two seminal studies on grapevine bud development. Using Self-Organizing Maps, we parsed the combined gene expression data into three major clusters corresponding to distinct seasonal activities, which we termed "summer-upregulated," "winter-upregulated," and "intermediate." Our analysis revealed that genes whose expression was predominantly upregulated during the winter months were significantly enriched in Gene Ontology terms related to stilbenoid biosynthesis and thiamine biosynthesis. This finding prompted a deeper investigation into these two pathways. We observed profound and coordinated upregulation of key genes in both pathways during the coldest winter months, suggesting that these genes are integral components of the bud's strategy for surviving low temperatures and maintaining viability. These results confirm the role of stilbenoids as stress-responsive compounds and reveal a novel role for thiamine biosynthesis in the molecular mechanisms of grapevine bud dormancy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12870-026-08190-w.

Authors: T. Konecny, A. Asatryan, H. Binder

Date Published: 21st Jan 2026

Publication Type: Journal

Spatial transcriptome analysis of the human eyelid depicts meibomian gland cell differentiation: A pilot study.

Abstract (Expand)

Meibomian glands (MGs) are an integral component of the ocular defense system, as their secretion product, meibum, is essential for protecting the eye surface. To characterize the transcriptional program … underlying meibum production, we employed spatial transcriptomics (ST) analysis of the human eyelid from a sample from a 60-year-old male. We resolved 18 distinct eyelid clusters, representing structures such as the conjunctiva, epidermis, hair-associated sebaceous glands, and MGs. Focusing on the MG, we distinguished basal (MEI-B cluster) and differentiating (MEI-DIFF cluster) meibocytes, as well as a third, duct-related cluster (MEI-DUCT). Self-organizing maps (SOM) portrayal of ST images and pseudotime analysis confirmed progress from MEI-B to MEI-DIFF and further to MEI-DUCT, as the latter turned out to include terminally differentiated meibocytes. Accordingly, gene set enrichment analysis associated early/intermediate meibocyte maturation with energy and lipid metabolism, and later stages with barrier functions. We also identified significant differences between the MG and sebaceous gland transcriptomes. The MG-specific signature included transcripts such as AQP9, MMP3, and PITX1, and selective expression of PITX1 in the MG compared to the sebaceous gland was confirmed by immunohistochemistry on the same sample and samples from three other elderly adults. We deliver the first spatial portrait of the human MG transcriptional landscape. Besides enhancing our understanding of MG physiology, our study identifies novel targets for regulating MG homeostasis in health and disease.

Authors: H. Binder, U. Hampel, H. Loeffler-Wirth, F. Hansmann, H. Pfannkuche, M. Schmidt, M. R. Schneider

Date Published: 19th Sep 2025

Publication Type: Journal

Responding to Stress: Diversity and Resilience of Grapevine in a Changing Climate Under the Perspective of Omics Research

Abstract (Expand)

hange, with its altered precipitation and extreme temperatures, significantly threatens global viticulture by affecting grapevine growth, yield, and fruit quality. Understanding the molecular underpinnings … of grapevine resilience is crucial for developing adaptive strategies. Our aim is to explore the application of multi-omics approaches (integrating genomics, transcriptomics, proteomics, metabolomics, and epigenetics) to investigate grapevine stress responses. Advances in these omics technologies have been pivotal in identifying key stress-response genes, metabolic pathways, and regulatory networks, particularly those contributing to grapevine tolerance to water deficiency, (such as drought and decreased precipitation), extreme temperatures, UV radiation, and salinity. Furthermore, the rich genetic reservoir within grapevines serves as a vital resource for enhancing stress tolerance. While adaptive strategies such as rootstock selection and precision irrigation are important, future research must prioritize integrated multi-omics studies, including those on regional climate adaptation and long-term breeding programs. Such efforts are essential to exploit genetic diversity and ensure the sustainability of viticulture in the evolving climate. In summary, this review demonstrates how utilizing the inherent genetic variability of grapevines and employing multi-omics approaches are critical for understanding and enhancing their resilience to the challenges posed by climate change.

Authors: Tomas Konecny, Armine Asatryan, Hans Binder

Date Published: 15th Aug 2025

Publication Type: Journal

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