Biology subjects

Ludwig, E.

Publications and source records attributed to Ludwig, E..

3 recordsLinked to original sources

bioRxiv2026

Integrin α10β1- selected mesenchymal stem cells are protective in a murine model of post-traumatic osteoarthritis

BackgroundPost-traumatic osteoarthritis (PT-OA) is a debilitating condition with significant unmet clinical need. Mesenchymal stem cells (MSCs) represent promising candidates for the treatment of cartilage conditions, owing to their immunomodulatory and regenerative capacities. However, the marked heterogeneity of MSC preparations remains a major challenge for product standardization and prediction of therapeutic efficacy. We previously identified integrin 10{beta}1 as a marker for the selection of a more homogenous MSC preparation, with cartilage repair potential in vivo. In this study, we evaluated the therapeutic efficacy of human MSCs selected for high integrin 10{beta}1 expression in a murine PT-OA model, and compared their effects with those of unselected MSCs. MethodsUnselected or integrin 10-selected human bone marrow MSCs were characterized by flow cytometry and differentiation potential into adipogenic, osteogenic and chondrogenic lineages. Cells encapsulated into fibrin gel were applied intra-articularly at the time of surgery in the destabilization of the medial meniscus (DMM) mouse model of PT-OA. Eight weeks after DMM induction, severity of cartilage damage was assessed on Safranin O-stained sections using the OARSI scoring system. Synovitis, periarticular chondrogenesis, and osteophyte formation were evaluated histologically. OA-associated proteases, extracellular matrix degradation markers, and apoptosis were analyzed by immunohistochemistry, ELISA, and TUNEL assay. Persistence of transplanted human cells was assessed by PCR. ResultsIntegrin 10{beta}1-selected MSCs showed the characteristic MSCs immunophenotype and trilineage differentiation capacity. In vivo, treatment with integrin 10-selected MSCs significantly attenuated PT-OA-induced articular cartilage degeneration compared with both unselected MSCs and vehicle-treated controls. Further histopathological analyses revealed tendency toward reduced synovitis and periarticular chondrogenesis. Moreover, integrin 10-selected MSC treatment was associated with modest reductions in apoptotic activity and decreased expression of OA-related proteases and extracellular matrix degradation markers. Lastly, human cells were not detectable in joint tissues at the study endpoint. ConclusionsIntegrin 10-selected MSCs demonstrated superior chondroprotective effects compared with unselected MSCs, highlighting their potential as a standardized and efficacious cell therapy for PT-OA. These findings further validate the feasibility and safety of selection and in vivo administration of MSCs with high expression of integrin 10.

molecular biology↗

bioRxiv2026

The grain amaranth pangenome reveals domestication-associated changes in diversity and function of structural variation

BackgroundGrain amaranth is a nutritious pseudocereal from the Americas that was independently domesticated three times from a common wild ancestor. The three domesticated grain amaranths, their wild progenitor, and a close wild relative form a species complex. Pangenomes enable the assessment of genetic variation beyond single nucleotide polymorphisms. ResultsWe have constructed a pangenome for the entire grain amaranth species complex, consisting of new, chromosome-scale genome assemblies for all five species, including the first reference genomes for A. caudatus and A. quitensis. Our high-quality assemblies reach near telomere-to-telomere contiguity. Comparative analyses within the grain amaranth pangenome revealed a high degree of collinearity and overall conserved chromosome structure across species. Genes are similarly conserved, with a [~]75% core gene set. We identify over 100,000 structural variants, distributed throughout the genomes. We quantify gene presence-absence and find that protein biosynthesis gene families were expanding during domestication, while gene loss reflects possible redundancies in other processes. We further map flowering time in a biparental population and find two QTL that together account for a 55-day difference in flowering time between homozygous genotypes. One QTL contains an ortholog of a known flowering-time regulator that may be disrupted by an insertion in the late flowering parent. ConclusionsOur work establishes high-quality genomic resources for the promising protein crop grain amaranth and sheds light on how structural variants shape genomic diversity and repeated evolutionary change in crops. The structural variants and flowering time loci identified can help to understand amaranth adaptation and provide breeding targets for crop improvement.

genomics↗

bioRxiv2022

Natural Variation in Brachypodium distachyon Responses to Combined Abiotic Stresses

The growing world population increases demand for agricultural production, which is more challenging as climate change increases global temperature and causes more extreme weather events. High-throughput phenotyping tools can be used to measure plant responses to the environment to identify genomic regions associated with response to stress. This study examines the phenotypic variation of 149 accessions of Brachypodium distachyon under drought, heat, and the combination of both stresses. Heat alone causes the largest amounts of tissue damage and the combination of heat and drought causes the largest decrease in plant biomass compared to other treatments. Notably, Bd21-0, the reference line for B. distachyon, was identified as not having very robust growth under stress conditions, especially in the heat-drought combined treatment. Climate data from the collection locations of these accessions (climate of origin) was used to assess whether climate of origin was correlated with responses to stresses and it was found to be significantly associated with height and percent of plant tissue damage. Additionally, genome wide association mapping found a number of genetic loci associated with changes in plant height, biomass, and the amount of damaged tissue under stress. Some SNPs found to be significantly associated with a response to heat or drought are also significantly associated in the combination of stresses, while others are not, and some significantly associated SNPs were only identified in the combined stress treatment. This, combined with the phenotypic data, indicates that the effects of these abiotic stresses are not simply additive, and the responses of B. distachyon to the combined stresses differ from drought and heat alone. Significant SNPs were closely located to genes known to be involved in plant responses to abiotic stresses.

plant biology↗