Results and Problems in Cell Differentiation最新文献

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.

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.

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.

It has long been assumed that a specific cell type arises following stepwise specification of cells corresponding to the branching of cell lineages. However, accumulating evidence indicates that multiple and even remote cell lineages can lead to the development of the same cells. Four examples giving different yet new insights will be discussed: skeletal muscle development from precursors with distinct initial histories of transcriptional regulation, lens cell development from remote lineages yet sharing basic transcription factors, blood cell development under intersectional pathways, and neural tissue development from cardiac precursors through the manipulation of just one component of epigenetic regulation. These examples provide flexible and nondogmatic perspectives on developmental cell regulation, fundamentally revising the old model relying on cell lineages.

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.

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.

Cell-cell fusion is a normal physiological mechanism that requires a well-orchestrated regulation of intracellular and extracellular factors. Dysregulation of this process could lead to diseases such as osteoporosis, malformation of muscles, difficulties in pregnancy, and cancer. Extensive literature demonstrates that fusion occurs between cancer cells and other cell types to potentially promote cancer progression and metastasis. However, the mechanisms governing this process in cancer initiation, promotion, and progression are less well-studied. Fusogens involved in normal physiological processes such as syncytins and associated factors such as phosphatidylserine and annexins have been observed to be critical in cancer cell fusion as well. Some of the extracellular factors associated with cancer cell fusion include chronic inflammation and inflammatory cytokines, hypoxia, and viral infection. The interaction between these extracellular factors and cell's intrinsic factors potentially modulates actin dynamics to drive the fusion of cancer cells. In this review, we have discussed the different mechanisms that have been identified or postulated to drive cancer cell fusion.