Zebrafish Danio rerio myotomal muscle structure and growth from a spatial transcriptomics perspective.

Fish exhibit different muscle structures and growth characteristics compared with mammals. We used a spatial transcriptomics approach and examined myotomal muscle sections from zebrafish. Adult muscles were divided into eight regions according to spatial gene expression characteristics. Slow muscle was located in the wedge-shaped region near the lateral line and at the base of the dorsal fin, intermediate muscle was located in a ribbon-shaped region adjacent to slow muscle, and fast muscle was located in the deep region of the trunk, surrounded by intermediate muscle; the interior of fast muscle was further divided into 6 parts by their transcriptomic features. Combined analysis of adult and larval data revealed that adult muscles contain specific regions similar to larval muscles. These regions showed active myogenesis and a high expression of genes associated with muscle hyperplasia. This is the first study to apply spatial transcriptomics to fish myotomal muscle structure and growth.

Heart failure promotes multimorbidity through innate immune memory.

Patients with heart failure (HF) often experience repeated acute decompensation and develop comorbidities such as chronic kidney disease and frailty syndrome. Although this suggests pathological interaction among comorbidities, the mechanisms linking them are poorly understood. Here, we identified alterations in hematopoietic stem cells (HSCs) as a critical driver of recurrent HF and associated comorbidities. Bone marrow transplantation from HF-experienced mice resulted in spontaneous cardiac dysfunction and fibrosis in recipient mice, as well as increased vulnerability to kidney and skeletal muscle insults. HF enhanced the capacity of HSCs to generate proinflammatory macrophages. In HF mice, global chromatin accessibility analysis and single-cell RNA-seq showed that transforming growth factor-ß (TGF-ß) signaling was suppressed in HSCs, which corresponded with repressed sympathetic nervous activity in bone marrow. Transplantation of bone marrow from mice in which TGF-ß signaling was inhibited similarly exacerbated cardiac dysfunction. Collectively, these results suggest that cardiac stress modulates the epigenome of HSCs, which in turn alters their capacity to generate cardiac macrophage subpopulations. This change in HSCs may be a common driver of repeated HF events and comorbidity by serving as a key carrier of "stress memory."

A universal sequencing read interpreter.

Massively parallel DNA sequencing has led to the rapid growth of highly multiplexed experiments in biology. These experiments produce unique sequencing results that require specific analysis pipelines to decode highly structured reads. However, no versatile framework that interprets sequencing reads to extract their encoded information for downstream biological analysis has been developed. Here, we report INTERSTELLAR (interpretation, scalable transformation, and emulation of large-scale sequencing reads) that decodes data values encoded in theoretically any type of sequencing read and translates them into sequencing reads of another structure of choice. We demonstrated that INTERSTELLAR successfully extracted information from a range of short- and long-read sequencing reads and translated those of single-cell (sc)RNA-seq, scATAC-seq, and spatial transcriptomics to be analyzed by different software tools that have been developed for conceptually the same types of experiments. INTERSTELLAR will greatly facilitate the development of sequencing-based experiments and sharing of data analysis pipelines.

DNA-GPS: A theoretical framework for optics-free spatial genomics and synthesis of current methods.

While single-cell sequencing technologies provide unprecedented insights into genomic profiles at the cellular level, they lose the spatial context of cells. Over the past decade, diverse spatial transcriptomics and multi-omics technologies have been developed to analyze molecular profiles of tissues. In this article, we categorize current spatial genomics technologies into three classes: optical imaging, positional indexing, and mathematical cartography. We discuss trade-offs in resolution and scale, identify limitations, and highlight synergies between existing single-cell and spatial genomics methods. Further, we propose DNA-GPS (global positioning system), a theoretical framework for large-scale optics-free spatial genomics that combines ideas from mathematical cartography and positional indexing. DNA-GPS has the potential to achieve scalable spatial genomics for multiple measurement modalities, and by eliminating the need for optical measurement, it has the potential to position cells in three-dimensions (3D).

Age-Associated Different Transcriptome Profiling in Zebrafish and Rats: an Insight into the Diversity of Vertebrate Aging.

Most mammals, including humans, show obvious aging phenotypes, for example, loss of tissue plasticity and sarcopenia. In this regard, fish can be attractive models to study senescence because of their unique aging characteristics. The lifespan of fish varies widely, and several species can live for over 200 years. Moreover, some fish show anti-aging features and indeterminate growth throughout their life. Therefore, exploring the aging mechanism in fish could provide new insights into vertebrate aging. To this end, we conducted RNA sequencing (RNA-seq) assays for various organs and growth stages of zebrafish and compared the data with previously published RNA-seq data of rats. Age-associated differentially expressed genes (DEGs) for all zebrafish tissue samples reveal the upregulation of circadian genes and downregulation of hmgb3a. On one hand, a comparative analysis of DEG profiles associated with aging between zebrafish and rats identifies upregulation of circadian genes and downregulation of collagen genes as conserved transcriptome changes. On the other hand, in zebrafish, upregulation of autophagy-related genes in muscles and AP-1 transcription factor genes in various tissues is observed, which may imply fish-specific anti-aging characteristics. Consistent with our knowledge of mammalian aging, DEG profiles related to tissue senescence are observed in rats. We also detect age-associated downregulation of muscle homeostasis and differentiation-related genes in zebrafish gills, indicating a fish-specific senescence phenotype. Our results indicate both common and different aging profiles between fish and mammals, which could be used for future translational research.

Deep distributed computing to reconstruct extremely large lineage trees.

Phylogeny estimation (the reconstruction of evolutionary trees) has recently been applied to CRISPR-based cell lineage tracing, allowing the developmental history of an individual tissue or organism to be inferred from a large number of mutated sequences in somatic cells. However, current computational methods are not able to construct phylogenetic trees from extremely large numbers of input sequences. Here, we present a deep distributed computing framework to comprehensively trace accurate large lineages (FRACTAL) that substantially enhances the scalability of current lineage estimation software tools. FRACTAL first reconstructs only an upstream lineage of the input sequences and recursively iterates the same produce for its downstream lineages using independent computing nodes. We demonstrate the utility of FRACTAL by reconstructing lineages from >235 million simulated sequences and from >16 million cells from a simulated experiment with a CRISPR system that accumulates mutations during cell proliferation. We also successfully applied FRACTAL to evolutionary tree reconstructions and to an experiment using error-prone PCR (EP-PCR) for large-scale sequence diversification.