A non-coding variant linked to metabolic obesity with normal weight affects actin remodelling in subcutaneous adipocytes

Glunk, Viktoria; Laber, Samantha; Sinnott-Armstrong, Nasa; Sobreira, Débora R.; Strobel, Sophie; Batista, Thiago M.; Kubitz, Phil; Moud, Bahareh Nemati; Ebert, Hannah; Huang, Yongjun; Brandl, Beate; Garborcauskas, Garrett; Honecker, Julius; Stirling, David R.; Abdennur, Nezar; Calabuig-Navarro, Virtu; Skurk, Thomas; Ocvirk, Soeren; Stemmer, Kerstin; Cimini, Beth A.; Carpenter, Anne E.; Dankel, Simon N.; Lindgren, Cecilia M.; Hauner, Hans; Nóbrega, Marcelo A.; Claussnitzer, Melina

doi:10.1038/s42255-023-00807-w

Cited by 10 publications

(2 citation statements)

References 89 publications

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“…This cluster, along with cluster 4 (putative adipocyte precursor cells), also highly expressed ebf1 , which is involved in adipocyte differentiation (26). An additional marker gene for cluster 1 was cobll1 (27), which is highly expressed in adipose-derived MSCs. The proportion of cells in cluster 1 (MSCs) was greater than that in cluster 3 (fibroblasts).…”

Section: Resultsmentioning

confidence: 99%

Characterisation of mesenchymal stromal cells in the skin of Atlantic salmon

Ruiz Daniels,

Salisbury,

Sveen

et al. 2024

Preprint

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BackgroundThe skin serves as the first line of defence for an organism against the external environment. Despite the global significance of salmon in aquaculture, a critical component of this first line of defence, mesenchymal stromal cells, remains unexplored. These pluripotent cells can differentiate into various tissues, including bone, cartilage, tendon, ligament, adipocytes, dermis, muscle and connective tissue within the skin. These cells are pivotal for preserving the integrity of skin tissue throughout an organism’s lifespan and actively participate in wound healing processes.ResultsIn this study, we characterise mesenchymal stromal cells in detail for the first time in healthy Atlantic salmon tissue and during the wound healing process. Single-nucleus sequencing and spatial transcriptomics revealed the transcriptional dynamics of these cells, elucidating the differentiation pathways leading to osteogenic and fibroblast lineages in the skin of Atlantic salmon. We charted their activity during an in vivo wound healing time course, showing clear evidence of their active role during this process, as they become transcriptionally more active during the remodelling stage of wound healing.ConclusionsFor the first time, we chart the activity of sub-clusters of differentiating stromal cells during the process of wound healing, revealing different spatial niches of the various MSC subclusters, and setting the stage for investigations into the manipulation of MSCs to improve fish health.

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Section: Resultsmentioning

confidence: 99%

Characterisation of mesenchymal stromal cells in the skin of Atlantic salmon

Ruiz Daniels,

Salisbury,

Sveen

et al. 2024

Preprint

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“…Genome-wide association studies (GWAS) have to a large extent contributed to an improved understanding of the genetic architecture of common obesity and have provided hundreds of novel risk variants [ 13 – 15 ]. However, although significant advances have been made in describing the mechanistic circuitry for a least some of these genetic variants [ 16 , 17 ], identifying novel risk variants in general precedes the biological and functional understanding of how these variants act in a certain target tissue in order to increase body weight. Furthermore, the variability of BMI attributed to genetic variation is still poorly explained [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Genetics and Epigenetics in Obesity: What Do We Know so Far?

Keller,

Svensson,

Rohde-Zimmermann

et al. 2023

Curr Obes Rep

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Purpose of Review Enormous progress has been made in understanding the genetic architecture of obesity and the correlation of epigenetic marks with obesity and related traits. This review highlights current research and its challenges in genetics and epigenetics of obesity. Recent Findings Recent progress in genetics of polygenic traits, particularly represented by genome-wide association studies, led to the discovery of hundreds of genetic variants associated with obesity, which allows constructing polygenic risk scores (PGS). In addition, epigenome-wide association studies helped identifying novel targets and methylation sites being important in the pathophysiology of obesity and which are essential for the generation of methylation risk scores (MRS). Despite their great potential for predicting the individual risk for obesity, the use of PGS and MRS remains challenging. Summary Future research will likely discover more loci being involved in obesity, which will contribute to better understanding of the complex etiology of human obesity. The ultimate goal from a clinical perspective will be generating highly robust and accurate prediction scores allowing clinicians to predict obesity as well as individual responses to body weight loss-specific life-style interventions.

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