The chromatin architecture of mammalian genomes exhibits a complex, multilayered three-dimensional structure. The spatial folding of chromosomes and their organization in the nucleus have profound effects on gene expression and cellular function, and changes in nuclear organization affect both normal development and various diseases. Investigating the three-dimensional organization of DNA within the nucleus, along with its temporal dynamics, constitutes a primary focus of research in the 4D Nucleome Project. This special issue provides comprehensive reviews of technological advances to investigate the 3D organization of the DNA in the nucleus and the functional implication of 4D Nucleome in physiology and human disease.

Mucosal tissues, including the respiratory, digestive, urinary, and skin, are crucial barriers against external pathogens. Beyond their physical barrier function, mucosal membranes foster a symbiotic relationship with commensal bacteria, contributing to the body's ecological balance. The mucosal immune system plays a pivotal role in maintaining immunological homeostasis and orchestrating interactions between innate and acquired immunity. Recent research has highlighted the importance of innate lymphocytes, including innate lymphoid cells (ILCs), γδ T cells, and CD1-restricted T cells, in immune homeostasis and responses to antigens or allergens within mucosal tissues. These specialized immune cells have unique activation modes and functions, presenting opportunities for novel therapeutic interventions in immune-related diseases. This special issue aims to provide comprehensive reviews of their activation mechanisms, functions, and potential as therapeutic targets for diverse immune disorders.

The regulation of cell death is an important process in maintaining tissue homeostasis in organs and is associated with a variety of physiological and pathological conditions. In addition to the well-defined necrosis and apoptosis, several new types of cell death processes have been identified, such as pyroptosis, necroptosis, and ferroptosis. To develop therapeutic tools for cancer, immune diseases, infections and metabolic pathologies, it is essential to understand the role of different regulators and effectors of each cell death process. Therefore, in this special issue, we review several recent studies on the regulation of different types of cell death and their role in health and disease. We also discuss recent trends in cell death to improve our understanding of the role of different types of cell death pathways.

RNA therapy is defined as the use of RNA-based molecules to prevent or treat disease. As recent research has shown, the field of RNA therapy has made significant advances. In particular, the ability to target diverse genetic materials in the body and the rapid development of drugs is why we can expect to see more research efforts focused on developing RNA-based therapeutics in the future. In this special issue, we have selected some of the most important topics related to RNA therapy. We cover the latest microRNA (miRNA) therapeutics in clinical trials, the latest efforts to deliver small interfering RNAs (siRNAs) to diverse organs, the disease association of RNA fragments derived from transfer RNAs (tRNAs), and the immune response induced by messenger RNA (mRNA) vaccines, which has received much attention. The combination of research in these different areas will enable us to overcome a range of diseases that were previously difficult to treat or prevent.

The transcriptomic plasticity conferred by post-transcriptional regulation is a fundamental mechanism driving the diversity of proteomes in biological systems. Similar to epigenetic modifications on DNA and histone proteins, RNA is also subject to various chemical modifications, called epitranscriptomic modifications. Notably, recent studies suggested that epitranscriptomic modifications influence almost all aspects of RNA metabolism, including stability, splicing, localization, and translation, enabling precise and flexible control of gene expression. The special issue provides comprehensive reviews of technological advances to investigate the epitranscriptome and the functional contribution of epitranscriptomic regulations in different physiological contexts and the status of human diseases. Guest Editor: Ki-Jun Yoon, Korea Advanced Institute of Science and Technology (KAIST), Korea Submission Guideline: https://www.nature.com/documents/emm-gta.pdf

All constituents of living organisms (e.g., DNAs, RNAs, proteins, lipids, lactate, other metabolites) are in a constant state of turnover at varying rates to achieve overall “dynamic” homeostasis. This dynamic nature of metabolism of biomolecules in fully assembled living organisms cannot be accurately revealed by the measurements of static, snapshot infor¬mation (“statomics”) on metabolisms such as transcriptomics, proteomics, metabolomics, and cellular signaling cascades, which often failed to reflect actual metabolic status. Combined approaches of fluxomics and “statomics” in vivo can provide an in-depth dynamic assessment of metabolic alterations, as well as simultaneous explorations of the molecular basis for the observed kinetic responses that enables a better understanding of the metabolic status of living organism and thus leading to discovery and development of effective therapeutics. In this Special Features, the reviews are written by experts in the field of tracer methodology or fluxomics that reveals the dynamic status of metabolism in vivo and deal with the basic principles and applications of the methodologies to various metabolic research fields (e.g., protein, lipid, lactate, and other nutrient metabolism in relation to normal and pathophysiology).

Over last decades obese populations continue to increase worldwide and obesity-related diseases will be an increasing threat to human health unless we find effective ways to prevent and manage obesity. Understanding the mechanisms underlying weight control is essential for our effects to combat obesity. The mammals evolve to develop the system for energy homeostasis. The center for this system resides in the hypothalamus. The hypothalamus is connected to a number of brain regions and peripheral organs via complex neural circuits including the autonomic nervous system. Feeding behaviors and energy expenditure are elaborately controlled through their communications. Remarkable advances in neuroscience and genetic technology enable us to discover specific neuronal populations and their neural circuits involved in various steps of feeding behaviors as well as control of energy and glucose metabolism. The brain-gut axis is attractable and more approachable in the aspect of obesity treatment. Recent studies highlight the roles of gut, gut-derived hormones, and gut-resident microbiota in energy metabolism and obesity. Although genetic factors considerably affect obesity development, environmental factors during developmental and post-developmental periods, especially overconsumption of fat-rich diets, promotes obesity by disrupting neural mechanisms maintaining energy homeostasis. The detailed pathological processes and critical mediators underpinning diet-induced obesity are beginning to be revealed. This special review series update you on a recent progress in neural mechanisms of weight control in relation to obesity. Guest Editors: Il-Young Kim, Gachon University College of Medicine, Korea Robert R. Wolfe, University of Arkansas for Medical Sciences, USA Submission Guideline: https://www.nature.com/documents/emm-gta.pdf

Over the last decade, adult stem cell-derived organoid systems have extended into diverse fields of biomedical science: the applications range from use as a model system for the basic biology of internal organs to a new platform for human biology, enabling the live biobanking of patient samples of cancer and other diseases, genetic engineering, image-based screening, genomics and studies of infection biology. Despite the rapid progress of the field, organoid technology has thus far been utilized only by a few leading laboratories and early adopters. It often takes years of trial and error to set up, since the cultures depend on complex growth factor cocktails, the handling of organoids needs extensive training, and obtaining human samples requires ethical permissions and collaboration with clinicians. More importantly, the potential of the system will not be fully realized while unpublished know-how and trade secrets form a barrier for newcomers to the field. In this special issue, a group of expert teams have therefore made a joint effort to share the methodological details of various organoid applications. With this special issue, I wish to invite more people to join the organoid community and to adopt this state-of-the-art technology to explore their own biological questions. Guest Editor: Bon-Kyoung Koo, Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Austria Submission Guideline: https://www.nature.com/documents/emm-gta.pdf

In the 21st century, the rapidly changing global landscape have accelerated the emergence and spread of novel viral pathogens. Emerging zoonotic viral diseases pose a constant threat, and the appearance of a new virus or reemergence of a previously identified virus with diversified properties is cause for global concern. The current pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and other viral disease outbreaks, such as those of tick-borne SFTS and human infections with avian influenza viruses, serve as a constant reminder of how vulnerable humans are to emerging viral pathogens. The threat to public health posed by the emergence of novel fatal viral diseases has driven concentrated efforts to understand viral molecular and cellular biology. However, despite the attempts to elucidate the complexities of these emerging viruses, scant new information regarding the ever-changing threats posed by these viruses exists. This special issue provides a comprehensive review of emerging viral diseases. This information is an invaluable resource for those seeking to understand the mechanisms underlying host-virus interactions, which is necessary for controlling emerging fatal viral diseases, and provides insights into potential future pandemics. Guest Editor: Young Ki Choi, Chungbuk National University, Korea Submission Guideline: https://www.nature.com/documents/emm-gta.pdf

Technical advancements in single-cell genomics have improved our understanding of molecular and genetic regulation. All cell types in the human body can now be characterized using single-cell multi-omics analyses, which help uncover the complex genetic and epigenetic regulatory mechanisms and indicate cellular interactions within tissues. Now, as single-cell research moves toward clinical implementation, it is being incorporated in diagnostic and therapeutic measures for precision medicine. This special issue in single-cell genomics provides a comprehensive view of the current technological status and the future perspectives and applications of single-cell analysis.

Host-microbiome interactions have been demonstrated to influence various aspects of human biology in health and disease. Microbes are involved in the development and fine-tuning of the immune system, as well as various pathologies, such as gut inflammation, neurological disorders and cancers. Thus, microbes, microbial products and their interactions within the microbial community and with the host provide immense opportunities for therapeutic modulation. However, the field is still at the foundational level, and to advance precision microbiome-based medicine, extensive scientific evidence will be required. In this special issue of EMM, we present a collection of review articles on human-microbiome interactions affecting factors involved in symbiosis to develop microbiome therapeutics.

Population ageing will likely lead to an increase in the prevalence of bone diseases such as osteoporosis and osteoarthritis, thereby increasing the financial burden among both diseased and unaffected people. Although significant progress has been made in understanding bone health in biomedical applications, more research is needed to address unmet needs and understand healthy bone homeostasis. This special issue of Experimental & Molecular Medicine includes a collection of review articles on cutting-edge topics related to healthy bone homeostasis.