Mouse (Mus musculus) models have been heavily utilized in developmental biology research to understand mammalian embryonic development, as mice share many genetic, physiological, and developmental characteristics with humans. New explorations into the integration of temporal (stage-specific) and transcriptional (tissue-specific) data have expanded our knowledge of mouse embryo tissue-specific gene functions. To better understand the substantial impact of synonymous mutational variations in the cell-state-specific transcriptome on a tissue\'s codon and codon pair usage landscape, we have established a novel resource-Mouse Embryo Codon and Codon Pair Usage Tables (Mouse Embryo CoCoPUTs). This webpage not only offers codon and codon pair usage, but also GC, dinucleotide, and junction dinucleotide usage, encompassing four strains, 15 murine embryonic tissue groups, 18 Theiler stages, and 26 embryonic days. Here, we leverage Mouse Embryo CoCoPUTs and employ the use of heatmaps to depict usage changes over time and a comparison to human usage for each strain and embryonic time point, highlighting unique differences and similarities. The usage similarities found between mouse and human central nervous system data highlight the translation for projects leveraging mouse models. Data for this analysis can be directly retrieved from Mouse Embryo CoCoPUTs. This cutting-edge resource plays a crucial role in deciphering the complex interplay between usage patterns and embryonic development, offering valuable insights into variation across diverse tissues, strains, and stages. Its applications extend across multiple domains, with notable advantages for biotherapeutic development, where optimizing codon usage can enhance protein expression; one can compare strains, tissues, and mouse embryonic stages in one query. Additionally, Mouse Embryo CoCoPUTs holds great potential in the field of tissue-specific genetic engineering, providing insights for tailoring gene expression to specific tissues for targeted interventions. Furthermore, this resource may enhance our understanding of the nuanced connections between usage biases and tissue-specific gene function, contributing to the development of more accurate predictive models for genetic disorders.

A significant role of the plant is played by the transcription factor FARL, which is light signal transduction as well as plant growth and development. Despite being transposases, FARL has developed a variety of dominant biological actions in evolution and speciation. On the other hand, little is known about the Zea mays FARL protein family. This study identifies and characterizes fifteen ZmFARL genes genome-wide, and RNA sequencing data was used to profile their expression. 105 FARL proteins from five plant species were classified into five groups based on sequence alignment and phylogeny. The ZmFARL genes\' exon-intron and motif distribution were conserved based on their evolutionary group. The fifteen ZmFARL genes were distributed over seven of the ten Z. mays chromosomes, although no duplication was discovered. Cis-element analysis reveals that ZmFARL genes play a variety of activities, including tissue-specific, stress- and hormone-responsive expressions. Furthermore, the results of the RNA sequencing used to profile expression showed that the genes ZmFARL2 and ZmFARL5 were much more expressed than other genes in various tissues, particularly in leaf characteristics. The identification of likely genes involved in cellular activity in Z. mays and related species will be aided by the characterization of the FARL genes.

Protein therapeutics play a critical role in treating a large variety of diseases, ranging from infections to genetic disorders. However, their delivery to target tissues beyond the liver, such as the lungs, remains a great challenge. Here, we report a universally applicable strategy for lung-targeted protein delivery by engineering Lung-Specific Supramolecular Nanoparticles (LSNPs). These nanoparticles are designed through the hierarchical self-assembly of metal-organic polyhedra (MOP), featuring a customized surface chemistry that enables protein encapsulation and specific lung affinity after intravenous administration. Our design of LSNPs not only addresses the hurdles of cell membrane impermeability of protein and nonspecific tissue distribution of protein delivery, but also shows exceptional versatility in delivering various proteins, including those vital for anti-inflammatory and CRISPR-based genome editing to the lung, and across multiple animal species, including mice, rabbits, and dogs. Notably, the delivery of antimicrobial proteins using LSNPs effectively alleviates acute bacterial pneumonia, demonstrating a significant therapeutic potential. Our strategy not only surmounts the obstacles of tissue-specific protein delivery but also paves the way for targeted treatments in genetic disorders and combating antibiotic resistance, offering a versatile solution for precision protein therapy.

BACKGROUND: The genetic background of cancer remains complex and challenging to integrate. Many somatic mutations within genes are known to cause and drive cancer, while genome-wide association studies (GWAS) of cancer have revealed many germline risk factors associated with cancer. However, the overlap between known somatic driver genes and positional candidate genes from GWAS loci is surprisingly small. We hypothesised that genes from multiple independent cancer GWAS loci should show tissue-specific co-regulation patterns that converge on cancer-specific driver genes.
RESULTS: We studied recent well-powered GWAS of breast, prostate, colorectal and skin cancer by estimating co-expression between genes and subsequently prioritising genes that show significant co-expression with genes mapping within susceptibility loci from cancer GWAS. We observed that the prioritised genes were strongly enriched for cancer drivers defined by COSMIC, IntOGen and Dietlein et al. The enrichment of known cancer driver genes was most significant when using co-expression networks derived from non-cancer samples of the relevant tissue of origin.
CONCLUSIONS: We show how genes within risk loci identified by cancer GWAS can be linked to known cancer driver genes through tissue-specific co-expression networks. This provides an important explanation for why seemingly unrelated sets of genes that harbour either germline risk factors or somatic mutations can eventually cause the same type of disease.

UNASSIGNED: Pseudogenes are sequences that have lost the ability to transcribe RNA molecules or encode truncated but possibly functional proteins. While they were once considered to be meaningless remnants of evolution, recent researches have shown that pseudogenes play important roles in various biological processes. However, the studies of pseudogenes in the silkworm, an important model organism, are limited and have focused on single or only a few specific genes.
UNASSIGNED: To fill these gaps, we present a systematic genome-wide studies of pseudogenes in the silkworm.
UNASSIGNED: We identified the pseudogenes in the silkworm using the silkworm genome assemblies, transcriptome, protein sequences from silkworm and its related species. Then we used transcriptome datasets from 832 RNA-seq analyses to construct spatio-temporal expression profiles for these pseudogenes. Additionally, we identified tissue-specifically expressed and differentially expressed pseudogenes to further understand their characteristics. Finally, the functional roles of pseudogenes as lncRNAs were systematically analyzed.
UNASSIGNED: We identified a total of 4410 pseudogenes, which were grouped into 4 groups, including duplications (DUPs), unitary pseudogenes (Unitary), processed pseudogenes (retropseudogenes, RETs), and fragments (FRAGs). The most of pseudogenes in the domestic silkworm were generated before the divergence of wild and domestic silkworm, however, the domestication may also involve in the accumulation of pseudogenes. These pseudogenes were clearly divided into 2 cluster, a highly expressed and a lowly expressed, and the posterior silk gland was the tissue with the most tissue-specific pseudogenes (199), implying these pseudogenes may be involved in the development and function of silkgland. We identified 3299 lncRNAs in these pseudogenes, and the target genes of these lncRNAs in silkworm pseudogenes were enriched in the egg formation and olfactory function.
UNASSIGNED: This study replenishes the genome annotations for silkworm, provide valuable insights into the biological roles of pseudogenes. It will also contribute to our understanding of the complex gene regulatory networks in the silkworm and will potentially have implications for other organisms as well.

Hydrogels derived from decellularized extracellular matrices (ECM) of animal origin show immense potential for regenerative applications due to their excellent cytocompatibility and biomimetic properties. Despite these benefits, the impact of decellularization protocols on the properties and immunogenicity of these hydrogels remains relatively unexplored. In this study, porcine skeletal muscle ECM (smECM) underwent decellularization using mechanical disruption (MD) and two commonly employed decellularization detergents, sodium deoxycholate (SDC) or Triton X-100. To mitigate immunogenicity associated with animal-derived ECM, all decellularized tissues were enzymatically treated with α-galactosidase to cleave the primary xenoantigen-the α-Gal antigen. Subsequently, the impact of the different decellularization protocols on the resultant hydrogels was thoroughly investigated. All methods significantly reduced total DNA content in hydrogels. Moreover, α-galactosidase treatment was crucial for cleaving α-Gal antigens, suggesting that conventional decellularization methods alone are insufficient. MD preserved total protein, collagen, sulfated glycosaminoglycan, laminin, fibronectin, and growth factors more efficiently than other protocols. The decellularization method impacted hydrogel gelation kinetics and ultrastructure, as confirmed by turbidimetric and scanning electron microscopy analyses. MD hydrogels demonstrated high cytocompatibility, supporting satellite stem cell recruitment, growth, and differentiation into multinucleated myofibers. In contrast, the SDC and Triton X-100 protocols exhibited cytotoxicity. Comprehensive in vivo immunogenicity assessments in a subcutaneous xenotransplantation model revealed MD hydrogels\' biocompatibility and low immunogenicity. These findings highlight the significant influence of the decellularization protocol on hydrogel properties. Our results suggest that combining MD with α-galactosidase treatment is an efficient method for preparing low-immunogenic smECM-derived hydrogels with enhanced properties for skeletal muscle regenerative engineering and clinical applications.

Transgene silencing is a common phenomenon observed in Caenorhabditis elegans, particularly in the germline, but the precise mechanisms underlying this process remain elusive. Through an analysis of the transcription factors profile of C. elegans, we discovered that the expression of several transgenic reporter lines exhibited tissue-specific silencing, specifically in the intestine of C. elegans. Notably, this silencing could be reversed in mutants defective in endogenous RNA interference (RNAi). Further investigation using knock-in strains revealed that these intestine-silent genes were indeed expressed in vivo, indicating that the organism itself regulates the intestine-specific silencing. This tissue-specific silencing appears to be mediated through the endo-RNAi pathway, with the main factors of this pathway, mut-2 and mut-16, are significantly enriched in the intestine. Additionally, histone modification factors, such as met-2, are involved in this silencing mechanism. Given the crucial role of the intestine in reproduction alongside the germline, the transgene silencing observed in the intestine reflects the self-protective mechanisms employed by the organisms. In summary, our study proposed that compared to other tissues, the transgenic silencing of intestine is specifically regulated by the endo-RNAi pathway.

Alzheimer\'s disease (AD) is a progressive neurodegenerative disorder that affects over 50 million elderly individuals worldwide. Although the pathogenesis of AD is not fully understood, based on current research, researchers are able to identify potential biomarker genes and proteins that may serve as effective targets against AD. This article aims to present a comprehensive overview of recent advances in AD biomarker identification, with highlights on the use of various algorithms, the exploration of relevant biological processes, and the investigation of shared biomarkers with co-occurring diseases. Additionally, this article includes a statistical analysis of key genes reported in the research literature, and identifies the intersection with AD-related gene sets from databases such as AlzGen, GeneCard, and DisGeNet. For these gene sets, besides enrichment analysis, protein-protein interaction (PPI) networks utilized to identify central genes among the overlapping genes. Enrichment analysis, protein interaction network analysis, and tissue-specific connectedness analysis based on GTEx database performed on multiple groups of overlapping genes. Our work has laid the foundation for a better understanding of the molecular mechanisms of AD and more accurate identification of key AD markers.

Although gene expression divergence has long been postulated to be the primary driver of human evolution, identifying the genes and genetic variants underlying uniquely human traits has proven to be quite challenging. Theory suggests that cell-type-specific cis-regulatory variants may fuel evolutionary adaptation due to the specificity of their effects. These variants can precisely tune the expression of a single gene in a single cell-type, avoiding the potentially deleterious consequences of trans-acting changes and non-cell type-specific changes that can impact many genes and cell types, respectively. It has recently become possible to quantify human-specific cis-acting regulatory divergence by measuring allele-specific expression in human-chimpanzee hybrid cells-the product of fusing induced pluripotent stem (iPS) cells of each species in vitro. However, these cis-regulatory changes have only been explored in a limited number of cell types. Here, we quantify human-chimpanzee cis-regulatory divergence in gene expression and chromatin accessibility across six cell types, enabling the identification of highly cell-type-specific cis-regulatory changes. We find that cell-type-specific genes and regulatory elements evolve faster than those shared across cell types, suggesting an important role for genes with cell-type-specific expression in human evolution. Furthermore, we identify several instances of lineage-specific natural selection that may have played key roles in specific cell types, such as coordinated changes in the cis-regulation of dozens of genes involved in neuronal firing in motor neurons. Finally, using novel metrics and a machine learning model, we identify genetic variants that likely alter chromatin accessibility and transcription factor binding, leading to neuron-specific changes in the expression of the neurodevelopmentally important genes FABP7 and GAD1. Overall, our results demonstrate that integrative analysis of cis-regulatory divergence in chromatin accessibility and gene expression across cell types is a promising approach to identify the specific genes and genetic variants that make us human.

The aging process is inherently complex, involving multiple mechanisms that interact at different biological scales. The nematode Caenorhabditis elegans is a simple model organism that has played a pivotal role in aging research following the discovery of mutations extending lifespan. Longevity pathways identified in C. elegans were subsequently found to be conserved and regulate lifespan in multiple species. These pathways intersect with fundamental hallmarks of aging that include nutrient sensing, epigenetic alterations, proteostasis loss, and mitochondrial dysfunction. Here we summarize recent data obtained in C. elegans highlighting the importance of studying aging at both the tissue and temporal scale. We then focus on the neuromuscular system to illustrate the kinetics of changes that take place with age. We describe recently developed tools that enabled the dissection of the contribution of the insulin/IGF-1 receptor ortholog DAF-2 to the regulation of worm mobility in specific tissues and at different ages. We also discuss guidelines and potential pitfalls in the use of these new tools. We further highlight the opportunities that they present, especially when combined with recent transcriptomic data, to address and resolve the inherent complexity of aging. Understanding how different aging processes interact within and between tissues at different life stages could ultimately suggest potential intervention points for age-related diseases.