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Biomedical subjects

Jörg Fuchs

Publications and source records attributed to Jörg Fuchs.

4 recordsLinked to original sources

CpG hypermethylation and WNT/AP-1 cooperativity define the epigenetic landscape and a clinical subgroup of high-risk pediatric adrenocortical carcinoma.

Pediatric adrenocortical tumors are rare, clinically heterogeneous neoplasms with unpredictable outcomes and limited treatment options. Through integrated multi-omic analysis of 214 pediatric adrenocortical tumors combining DNA methylation profiling, transcriptomics, chromatin accessibility, and spatial deconvolution, we identify four distinct risk groups. A high-risk subgroup is characterized by CpG island hypermethylation, chromosomal instability, and dismal survival. These tumors exhibit transcriptional co-activation of WNT signalling and activator protein-1 transcriptional programs and display balanced admixture of zona glomerulosa and zona fasciculata/reticularis-like cells. Spatial analysis reveals zona glomerulosa cells as WNT signaling hubs driving intercellular crosstalk. Mechanistically, the histone deacetylase inhibitor entinostat reverses promoter methylation, silences activator protein-1 activity, and induces apoptotic reprogramming in tumor models. These findings establish a molecular framework for risk stratification and identify actionable therapeutic vulnerabilities, providing an essential resource for studying this molecularly uncharted pediatric malignancy.

Humans

A haplotype-resolved pangenome of the barley wild relative Hordeum bulbosum.

Wild plants can contribute valuable genes to their domesticated relatives1. Fertility barriers and a lack of genomic resources have hindered the effective use of crop-wild introgressions. Decades of research into barley's closest wild relative, Hordeum bulbosum, a grass native to the Mediterranean basin and Western Asia, have yet to manifest themselves in the release of a cultivar bearing alien genes2. Here we construct a pangenome of bulbous barley comprising 10 phased genome sequence assemblies amounting to 32 distinct haplotypes. Autotetraploid cytotypes, among which the donors of resistance-conferring introgressions are found, arose at least twice, and are connected among each other and to diploid forms through gene flow. The differential amplification of transposable elements after barley and H. bulbosum diverged from each other is responsible for genome size differences between them. We illustrate the translational value of our resource by mapping non-host resistance to a viral pathogen to a structurally diverse multigene cluster that has been implicated in diverse immune responses in wheat and barley.

Hordeum

Does chromoanagenesis play a role in the origin of B chromosomes?

B chromosomes (Bs) exist in addition to the standard (A) chromosomes in a wide range of species. The process underlying their origin is still unclear. We propose pathways of intra- and interspecific origin of B chromosomes based on known mechanisms of chromosome evolution and available knowledge of their sequence composition in different species. We speculate that a mitotic or meiotic segregation error of one or more A chromosomes initiates, via chromoanagenesis, the formation of a proto-B chromosome. In the second step, proto-B chromosomes accumulate A chromosome- and organelle-derived sequences over time, most likely via DNA double-strand break (DSB) mis-repair. Consequently, the original structure of the early stage proto-B chromosomes becomes masked by continuous sequence incorporation. The similarity between A chromosome sequences integrated into B chromosomes and the original sequences on the donor chromosomes decreases over time if there is no selection pressure on these sequences on B chromosomes. However, besides chromoanagenesis, also other mechanisms leading to the formation of B chromosomes might exist.

Evolution, Molecular

Genome diversity and evolution of the duckweed section Alatae comprising diploids, polyploids, and interspecific hybrids.

The section Alatae of genus Lemna of the monocotyledonous aquatic duckweed family (Lemnaceae) consists of rather diverse accessions with unknown phylogeny and unclear taxonomic assignment. In contrast to other duckweeds, some Alatae accessions, in addition to mainly vegetative propagation, produce readily flowers and viable seeds. We analyzed the genomic diversity and phylogenetic relationship of 52 Alatae accessions. For this purpose, we applied multiple molecular and cytogenetic approaches, including plastid and nuclear sequence polymorphisms, chromosome counting, genome size determination, and genomic in situ hybridization in combination with geographic distribution. We uncovered ploidy variation, recurrent hybridization, and backcrosses between species and their hybrids. The latter successfully spread over three continents. The results elucidate the evolution of Alatae accessions and explain the difficult taxonomic assignment of distinct accessions. Our study might be an example for analogous studies to resolve the hitherto unclear relationships among accessions of the duckweed genera Wolffiella and Wolffia.

Araceae