Transposable elements (TEs) are common mobile genetic elements comprising several classes and making up the majority of eukaryotic genomes. The movement and accumulation of TEs has been a major force shaping the genes and genomes of most organisms. Most eukaryotic genomes are dominated by retrotransposons and minimal DNA transposon accumulation. The ‘copy and paste’ lifecycle of replicative transposition produces new genome insertions without excising the original element. Horizontal TE transfer among lineages is rare. TEs represent a reservoir of potential genomic instability and RNA-level toxicity. Many TEs appear static and nonfunctional, but some are capable of replicating and mobilising to new positions, and somatic transposition events have been observed. The overall structure of retrotransposons and the domains responsible for the phases of their replication are highly conserved in all eukaryotes. TEs are important drivers of species diversity and exhibit great variety in their structure, size and transposition mechanisms, making them important putative actors in evolution. Because TEs are abundant in plant genomes, various applications have been developed to exploit polymorphisms in TE insertion patterns, including conventional or anchored PCR, and quantitative or digital PCR with primers for the 5ʹ or 3ʹ junction. Alternatively, the retrotransposon junction can be mapped using high-throughput next-generation sequencing and bioinformatics. With these applications, TE insertions can be rapidly, easily and accurately identified, or new TE insertions can be found. This review provides an overview of the TE-based applications developed for plant species and assesses the contributions of TEs to the analysis of plants’ genetic diversity.

The sarcomeric troponin-tropomyosin complex is a critical mediator of excitation-contraction coupling, sarcomeric stability and force generation. We previously reported that induced pluripotent stem cellderived cardiomyocytes (iPSC-CMs) from patients with a dilated cardiomyopathy (DCM) mutation, troponin T (TnT)-R173W, display sarcomere protein misalignment and impaired contractility. Yet it is not known how TnT mutation causes dysfunction of sarcomere microdomains and how these events contribute to misalignment of sarcomeric proteins in presence of DCM TnT-R173W. Using a human iPSC-CM model combined with CRISPR/Cas9-engineered isogenic controls, we uncovered that TnT-R173W destabilizes molecular interactions of troponin with tropomyosin, and limits binding of PKA to local sarcomere microdomains. This attenuates troponin phosphorylation and dysregulates local sarcomeric microdomains in DCM iPSC-CMs. Disrupted microdomain signaling impairs MYH7mediated, AMPK-dependent sarcomere-cytoskeleton filament interactions and plasma membrane attachment. Small molecule-based activation of AMPK can restore TnT microdomain interactions, and partially recovers sarcomere protein misalignment as well as impaired contractility in DCM TnT-R173W iPSC-CMs. Our findings suggest a novel therapeutic direction targeting sarcomere-cytoskeleton interactions to induce sarcomere re-organization and contractile recovery in DCM.Sarcomeres are the basic contractile unit of cardiac cells, whose particularly specialized function depends on a highly organized structure. The troponin-tropomyosin (Tn-Tm) complex at sarcomeric thin filaments is a critical component for excitation-contraction coupling. Stability and anchoring of the Tn-Tm complex on sarcomeres is provided by binding of the troponin T (TnT) subunit to Tm and the troponin I subunit (TnI) on actin myofilaments. Tropomyosin (TPM) together with TnI regulates actin/myosin binding and ATPase function in presence of micromolar, cytocolic Ca 2+ , which is bound by the troponin C subunit (TnC). This highly sensitive mechanisms is fine-tuned by post-translational modifications, such as PKA-mediated phosphorylation of TnI. Mutations in the Tn-Tm complex lead to severe disease, such as dilated cardiomyopathy (DCM). DCM is featured by left ventricular dilatation, contractile dysfunction, and arrhythmias 1 and represents a frequent cause of heart failure. More than 25% of DCM cases are caused by inherited mutations, particularly in sarcomeric proteins 2 . Recently, human iPSC-derived cardiomyocytes (iPSC-CMs) have been utilized for human genetic disease modeling 3-6 and drug testing 7 . Here, we analyze a sarcomeric mutation in cardiac troponin T (TnT), TnT-R173W. This mutation is located within one of the two tropomyosin binding regions of TnT, the T1 domain 8 and was the first DCM mutation reported in a human patient-specific iPSC-derived cardiomyocyte model 9 . This report www.nature.com/scientificreports www.nature.com/scientificreports/ demonstrated DCM patient-specific iPSC-CMs to display mole...

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