Results and Problems in Cell Differentiation最新文献

Compartmentalization of cellular components is critical to the spatiotemporal and environmental regulation of biochemical activities inside a cell, ensures the proper division of cellular labor and resources, and increases the efficiency of metabolic processes. However, compartmentalization also poses a challenge as organelles often need to communicate across these compartments to complete reaction pathways. These communication signals are often critical aspects of the cellular response to changing environmental conditions. A central signaling hub in the cell, the nucleus communicates with mitochondria, lysosomes, the endoplasmic reticulum, and the Golgi body to ensure optimal organellar and cellular performance. Here we review different mechanisms by which these organelles communicate with the nucleus, focusing on anterograde and retrograde signaling of mitochondria, localization-based signaling of lysosomes, the unfolded protein response of the endoplasmic reticulum, and evidence for nucleus-Golgi signaling. We also include a brief overview of some less well-characterized mechanisms of communication between non-nuclear organelles.

Trogocytosis is the intercellular transfer of membrane and membrane-associated proteins between cells. Trogocytosis is an underappreciated phenomenon that has historically routinely been dismissed as an artefact. With a greater understanding of the process and the implications it has on biological systems, trogocytosis has the potential to become a paradigm changer. The presence on a cell of molecules they don't endogenously express can alter the biological activity of the cell and could also lead to the acquisition of new functions. To better appreciate this phenomenon, it is important to understand how these intercellular membrane exchanges influence the function and activity of the donor and the recipient cells. In this chapter, we will examine how the molecules acquired by trogocytosis influence the biology of a variety of systems including mammalian fertilization, treatment of hemolytic disease of the newborn, viral and parasitic infections, cancer immunotherapy, and immune modulation.

Diagnosing and then treating disease defines theranostics. The approach holds promise by facilitating targeted disease outcomes. The simultaneous analysis of finding the presence of disease pathophysiology while providing a parallel in treatment is a novel and effective strategy for seeking improved medical care. We discuss how theranostics improves disease outcomes is discussed. The chapter reviews the delivery of targeted therapies. Bioimaging techniques are highlighted as early detection and tracking systems for microbial infections, degenerative diseases, and cancers.

The liver fulfils a plethora of metabolic and immunological functions. Liver macrophages are a heterogeneous immune cell population with high plasticity and are important for maintaining normal liver function but are also critically involved in disease processes. In this chapter, we review the heterogeneity and multifaceted functions of hepatic macrophages in liver health and in disease conditions, including acute liver injury, chronic liver diseases, and hepatocellular carcinoma. Under homeostatic conditions, the tissue resident Kupffer cells are phagocytic cells that have important functions in immune surveillance, antigen presentation, and metabolic regulation while the roles of other populations such as capsular, peritoneal, or monocyte-derived macrophages in liver health are less clearly defined. Upon liver injury, Kupffer cell numbers are markedly reduced while monocyte-derived macrophages significantly expand and take critical roles in driving and resolving liver injury, including important pathogenic involvements in inflammation, fibrosis, and regeneration. They also create and maintain an immunosuppressive and immune-excluded microenvironment in hepatocellular carcinoma. Single-cell and spatial omics technologies are significantly expanding our understanding of the diversity and plasticity of macrophage populations under different conditions and enable the reliable identification of specific hepatic macrophage subsets. This knowledge can now be applied to dissect the exact contributions of distinct macrophage populations to disease processes and hopefully will pave the way for new therapeutic interventions.

Tunneling nanotubes (TNTs) are open-ended, membrane-encased extensions that connect neighboring cells. They have diameters up to 1 μm but are able to expand to convey large cargos. Lengths vary depending on the distance of the cells but have been reported to be capable of extending beyond 300 μm. They have actin cytoskeletons that are essential for their formation, and may or may not have microtubule networks. It is thought that thin TNTs lack microtubules, while thicker TNTs have microtubular highways that use motor proteins to convey materials, including proteins, mitochondria, and nanoparticles between cells. Specifically, the presence of dynein and myosin support trafficking of cargo in both directions. The purpose of these connections is to enable cells to work as a unit or to extend cell life by diluting cytotoxic agents or acquiring biological material needed to survive.

Many organs are composed of epithelial and mesenchymal tissue components. These two tissue component types develop via reciprocal interactions. However, for historical and technical reasons, the effects of the mesenchymal components on the epithelium have been emphasized. Well-documented examples are the regionally specific differentiation of the endoderm-derived primitive gut tube under the influence of surrounding mesenchyme. In contrast to a pile of reports on mesenchyme-derived signaling mechanisms, few studies have depicted the epithelial action in depth. This chapter highlights an example of an opposite action from the epithelial side, which was found in esophagus development.

Communication among cells is vital in multicellular organisms. Various structures and mechanisms have evolved over time to achieve the intricate flow of material and information during this process. One such way of communication is through tunnelling membrane nanotubes (TNTs), which were initially described in 2004. These TNTs are membrane-bounded actin-rich cellular extensions, facilitating direct communication between distant cells. They exhibit remarkable diversity in terms of structure, morphology, and function, in which cytoskeletal proteins play an essential role. Biologically, TNTs play a crucial role in transporting membrane components, cell organelles, and nucleic acids, and they also present opportunities for the efficient transmission of bacteria and viruses, furthermore, may contribute to the dissemination of misfolded proteins in certain neurodegenerative diseases. Convincing results of studies conducted both in vitro and in vivo indicate that TNTs play roles in various biomedical processes, including cell differentiation, tissue regeneration, neurodegenerative diseases, immune response and function, as well as tumorigenesis.

Macrophages are dynamic and plastic immune cells essential for tissue homeostasis and pathogen defense. Their cell cycle regulation is highly influenced by intrinsic and extrinsic signals facilitating rapid responses to infections and tissue damage. Dysregulation of their cell cycle leads to diseases like cancer and HIV. This chapter highlights aspects of the macrophage cell cycle crucial for the development of targeted therapies.

Enhancers are the primary regulatory DNA sequences in eukaryotes and are mostly located in the non-coding sequences of genes, namely, intergenic regions and introns. The essential characteristic of an enhancer is the ability to activate proximal genes, e.g., a reporter gene in a reporter assay, regardless of orientation, relative position, and distance from the gene. These characteristics are ascribed to the interaction (spatial proximity) of the enhancer sequence and the gene promoter via DNA looping, discussed in the latter part of this chapter.Developmentally regulated genes are associated with multiple enhancers carrying distinct cell and developmental stage specificities, which form arrays on the genome. We discuss the array of enhancers regulating the Sox2 gene as a paradigm. Sox2 enhancers are the best studied enhancers of a single gene in developmental regulation. In addition, the Sox2 gene is located in a genomic region with a very sparse gene distribution (no other protein-coding genes in ~1.6 Mb in the mouse genome), termed a "gene desert," which means that most identified enhancers in the region are associated with Sox2 regulation. Furthermore, the importance of the Sox2 gene in stem cell regulation and neural development justifies focusing on Sox2-associated enhancers.