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Biology subjects

Salamon, R. J.

Publications and source records attributed to Salamon, R. J..

3 recordsLinked to original sources

NetTracer3D Enables User-Friendly Analysis of Diverse Microscopic and Medical 3D Datasets

Recent advances in high-resolution imaging and spatial transcriptomics have enabled reconstruction of complex 3D tissue maps, providing unprecedented insights into cellular connectivity, organization, and tissue architecture. However, standardization challenges hinder integration, sharing, and analysis of these datasets across research communities. We developed NetTracer3D to simplify three-dimensional image analysis across diverse datasets. NetTracer3D is an integrated tool for defining, processing, and sharing 3D tissue maps with standardized data formats and interactive exploration capabilities. It provides three broadly applicable network analysis modalities: Connectivity networks for analyzing functional tissue units or cells connected via secondary structures such as nerves or vasculature; Branch Adjacency and Branchpoint networks for converting branched anatomical structures into analyzable representations; and Proximity networks for grouping structures by spatial relationships to identify cellular organization patterns. We demonstrate several use cases applying NetTracer3D to analyze multidimensional data from CODEX and label free Raman spectroscopy, multiscalar data encompassing subcellular and anatomical scales and a range of modalities. NetTracer3D was able to characterize neural relationships between functional tissue units in human and mouse kidneys and mouse bronchi. Branchpoint networks were used to identify vascular defects in human brain angiogram and define the innervation structure of a lymph node. Finally, we demonstrate how proximity networks characterize the tumor microenvironment in 3D light sheet cancer images and auto-detect cellular neighborhoods in multiplexed 2D CODEX datasets. Beyond network creation, NetTracer3D enables analysis, spatial statistics, and visual analytics tailored for volumetric tissue data. By establishing interoperable formats and analysis workflows, this work provides accessible and reproducible analytical tools for 3D spatial biology, enabling new discoveries of relationships between structure and physiology.

genomics↗

Integrated Proteomics Identifies Troponin I Isoform Switch as a Regulator of a Sarcomere-Metabolism Axis During Cardiac Regeneration

Adult mammalian cardiomyocytes have limited proliferative potential, and after myocardial infarction (MI), injured cardiac tissue is replaced with fibrotic scar rather than with functioning myocardium. In contrast, the neonatal mouse heart possesses a regenerative capacity governed by cardiomyocyte proliferation; however, a metabolic switch from glycolysis to fatty acid oxidation during postnatal development results in loss of this regenerative capacity. Interestingly, a sarcomere isoform switch also takes place during postnatal development where slow skeletal troponin I (ssTnI) is replaced with cardiac troponin I (cTnI). In this study, we first employ integrated quantitative bottom-up and top-down proteomics to comprehensively define the proteomic and sarcomeric landscape during postnatal heart maturation. Utilizing a cardiomyocyte-specific ssTnI transgenic mouse model, we found that ssTnI overexpression increased cardiomyocyte proliferation and the cardiac regenerative capacity of the postnatal heart following MI compared to control mice by histological analysis. Our global proteomic analysis of ssTnI transgenic mice following MI reveals that ssTnI overexpression induces a significant shift in the cardiac proteomic landscape. This shift is characterized by an upregulation of key proteins involved in glycolytic metabolism. Collectively, our data suggest that the postnatal TnI isoform switch may play a role in the metabolic shift from glycolysis to fatty acid oxidation during postnatal maturation. This underscores the significance of a sarcomere-metabolism axis during cardiomyocyte proliferation and heart regeneration.

developmental biology↗

Defining Cardiac Nerve Architecture During Development, Disease, and Regeneration

Cardiac nerves regulate neonatal mouse heart regeneration and are susceptible to pathological remodeling following adult injury. Understanding cardiac nerve remodeling can lead to new strategies to promote cardiac repair. Our current understanding of cardiac nerve architecture has been limited to two-dimensional analysis. Here, we use genetic models, whole-mount imaging, and three-dimensional modeling tools to define cardiac nerve architecture and neurovascular association during development, disease, and regeneration. Our results demonstrate that cardiac nerves sequentially associate with coronary veins and arteries during development. Remarkably, our results reveal that parasympathetic nerves densely innervate the ventricles. Furthermore, parasympathetic and sympathetic nerves develop synchronously and are intertwined throughout the ventricles. Importantly, the regenerating myocardium reestablishes physiological innervation, in stark contrast to the non-regenerating heart. Mechanistically, reinnervation during regeneration is dependent on collateral artery formation. Our results reveal how defining cardiac nerve remodeling during homeostasis, disease, and regeneration can identify new therapies for cardiac disease.

developmental biology↗