Results and Problems in Cell Differentiation

Osteoclasts are multinucleated bone-resorbing cells derived from the monocyte/macrophage lineage. The macrophage colony-stimulating factor/receptor activator of nuclear factor κB ligand (M-CSF/RANKL) signaling network governs the differentiation of precursor cells into fusion-competent mononucleated cells. Repetitive fusion of fusion-competent cells produces multinucleated osteoclasts. Osteoclasts are believed to die via apoptosis after bone resorption. However, recent studies have found that osteoclastogenesis in vivo proceeds by replacing the old nucleus of existing osteoclasts with a single newly differentiated mononucleated cell...

Evidence of fusion of somatic cells has been noted in health and in disease for more than a century. The most obvious but uncertain hallmark has been the presence of multiple nuclei in cells. Although multinucleated cells are found in normal and diseased tissues, the benefit or harm of such cells can be difficult to elucidate. Still more difficult however is the identification of mononuclear cells previously formed by fusion of somatic cells with one or more nuclei disposed. The later process can introduce mutations that promote viral diversification, cancer, and tissue senescence...

The origin of eukaryotic cells, and especially naturally occurring syncytial cells, remains debatable. While a majority of our biomedical research focuses on the eukaryotic result of evolution, our data remain limiting on the prokaryotic precursors of these cells. This is particularly evident when considering extremophile biology, especially in how the genomes of organisms in extreme environments must have evolved and adapted to unique habitats. Might these rapidly diversifying organisms have created new genetic tools eventually used to enhance the evolution of the eukaryotic single nuclear or syncytial cells? Many organisms are capable of surviving, or even thriving, in conditions of extreme temperature, acidity, organic composition, and then rapidly adapt to yet new conditions...

Fast growth and prodigious cellular outputs make fungi powerful tools in biotechnology. Recent modeling work has exposed efficiency gains associated with dividing the labor of transcription over multiple nuclei, and experimental innovations are opening new windows on the capacities and adaptations that allow nuclei to behave autonomously or in coordination while sharing a single, common cytoplasm. Although the motivation of our review is to motivate and connect recent work toward a greater understanding of fungal factories, we use the analogy of the assembly line as an organizing idea for studying coordinated gene expression, generally...

In animals and plants, multinucleate cells (syncytia and coenocytes) are essential in ontogeny and reproduction. Fuso-morphogenesis is the formation of multinucleated syncytia by cell-cell fusion, but coenocytes are formed as a result of mitosis without cytokinesis. However, in plants, coenocytes are more widespread than true syncytia. Except for articulated laticifers, most plant syncytia have a trophic function. Here, we summarize the results of histological, histochemical, and ultrastructural analyses of syncytia in the Utricularia species from the Lentibulariaceae family...

Placentation is the development of a temporary arrangement between the maternal uterus and blastocyst-derived placental tissues designed to transport nutrients, gases, and other products from the mother to the embryo and fetus. Placentation differs histologically among species, but all types of placentation share the common trait of utilizing highly complex cell-to-cell and tissue-to-tissue morphological and biochemical interactions to remodel the uterine-placental interface. An elegant series of electron microscopy (EM) images supports the classification of ovine placentation as synepitheliochorial, because uterine luminal epithelial (LE) cells are maintained at the uterine-placental interface through incorporation into trophoblast syncytial plaques...

During placentation, villous cytotrophoblast (CTB) stem cells proliferate and fuse, giving rise to the multinucleated syncytiotrophoblast (STB), which represents the terminally differentiated villous layer as well as the maternal-fetal interface. The syncytiotrophoblast is at the forefront of nutrient, gas, and waste exchange while also harboring essential endocrine functions to support pregnancy and fetal development. Considering that mitochondrial dynamics and respiration have been implicated in stem cell fate decisions of several cell types and that the placenta is a mitochondria-rich organ, we will highlight the role of mitochondria in facilitating trophoblast differentiation and maintaining trophoblast function...

The Drosophila trachea is an interconnected network of epithelial tubes, which delivers gases throughout the entire organism. It is the premier model to study the development of tubular organs, such as the human lung, kidney, and blood vessels. The Drosophila embryonic trachea derives from a series of segmentally repeated clusters. The tracheal precursor cells in each cluster migrate out in a stereotyped pattern to form primary branches. Thereafter, the neighboring branches need to fuse to form an interconnected tubular network...

Drosophila development begins as a syncytium. The large size of the one-cell embryo makes it ideal for studying the structure, regulation, and effects of the cortical actin cytoskeleton. We review four main steps of early development that depend on the actin cortex. At each step, dynamic remodelling of the cortex has specific effects on nuclei within the syncytium. During axial expansion, a cortical actomyosin network assembles and disassembles with the cell cycle, generating cytoplasmic flows that evenly distribute nuclei along the ovoid cell...

Syncytia are common in the animal and plant kingdoms both under normal and pathological conditions. They form through cell fusion or division of a founder cell without cytokinesis. A particular type of syncytia occurs in invertebrate and vertebrate gametogenesis when the founder cell divides several times with partial cytokinesis producing a cyst (nest) of germ line cells connected by cytoplasmic bridges. The ultimate destiny of the cyst's cells differs between animal groups. Either all cells of the cyst become the gametes or some cells endoreplicate or polyploidize to become the nurse cells (trophocytes)...

Germline cysts are syncytia formed by incomplete cytokinesis of mitotic germline precursors (cystoblasts) in which the cystocytes are interconnected by cytoplasmic bridges, permitting the sharing of molecules and organelles. Among animals, such cysts are a nearly universal feature of spermatogenesis and are also often involved in oogenesis. Recent, elegant studies have demonstrated remarkable similarities in the oogenic cysts of mammals and insects, leading to proposals of widespread conservation of these features among animals...

Gamete production in most animal species is initiated within an evolutionarily ancient multicellular germline structure, the germline cyst, whose interconnected premeiotic cells synchronously develop from a single progenitor arising just downstream from a stem cell. Cysts in mice, Drosophila, and many other animals protect developing sperm, while in females, cysts generate nurse cells that guard sister oocytes from transposons (TEs) and help them grow and build a Balbiani body. However, the origin and extreme evolutionary conservation of germline cysts remains a mystery...

Actin is a highly conserved protein in mammals. The actin dynamics is regulated by actin-binding proteins and actin-related proteins. Nuclear actin and these regulatory proteins participate in multiple nuclear processes, including chromosome architecture organization, chromatin remodeling, transcription machinery regulation, and DNA repair. It is well known that the dysfunctions of these processes contribute to the development of cancer. Moreover, emerging evidence has shown that the deregulated actin dynamics is also related to cancer...

In the cell nucleus, actin participates in numerous essential processes. Actin is involved in chromatin as part of specific ATP-dependent chromatin remodeling complexes and associates with the RNA polymerase machinery to regulate transcription at multiple levels. Emerging evidence has also shown that the nuclear actin pool controls the architecture of the mammalian genome playing an important role in its hierarchical organization into transcriptionally active and repressed compartments, contributing to the clustering of RNA polymerase II into transcriptional hubs...

Polarity is an intrinsic and fundamental property of unicellular organisms and, as well, of single cells in multicellular ones. It can be defined as asymmetric cell organization that is self-reinforced and maintained by appropriate signaling. While cellular polarity is widely studied at the membrane and cytoplasmic level, if and how it is transmitted to the nucleus is still a matter of research and discussion. However, there is growing evidence of polarity transmission from the cell to the nucleus. In this chapter, we discuss recent reports on nuclear polarity and involvement of potential molecular players including emerin, nesprins, and nuclear F-actin which may play a significant role in establishment of this phenomenon...

The nucleus is a complex organelle with functions beyond being a simple repository for genomic material. For example, its actions in biomechanical sensing, protein synthesis, and epigenomic regulation showcase how the nucleus integrates multiple signaling modalities to intricately regulate gene expression. This innate dynamism is underscored by subnuclear components that facilitate these roles, with elements of the nucleoskeleton, phase-separated nuclear bodies, and chromatin safeguarding by nuclear envelope proteins providing examples of this functional diversity...

Eukaryotic genomes maintain multiple copies of ribosomal DNA gene repeats in tandem arrays to provide sufficient ribosomal RNAs to make ribosomes. These DNA repeats are the most highly transcribed regions of the genome, with dedicated transcriptional machinery to manage the enormous task of producing more than 50% of the total RNA in a proliferating cell. The arrays are called nucleolar organizer regions (NORs) and constitute the scaffold of the nucleolar compartment, where ribosome biogenesis occurs. Advances in molecular and cellular biology have brought great insights into how these arrays are transcribed and organized within genomes...

The three-dimensional architecture of chromosomes, their arrangement, and dynamics within cell nuclei are still subject of debate. Obviously, the function of genomes-the storage, replication, and transcription of genetic information-has closely coevolved with this architecture and its dynamics, and hence are closely connected. In this work a scale-bridging framework investigates how of the 30 nm chromatin fibre organizes into chromosomes including their arrangement and morphology in the simulation of whole nuclei...

In this chapter, we discuss the nuclear organization and how it responds to different types of stress. A key component in these responses is molecular traffic between the different sub-nucleolar compartments, such as nucleoplasm, chromatin, nucleoli, and various speckle and body compartments. This allows specific repair and response activities in locations where they normally are not active and serve to halt sensitive functions until the stress insult passes and inflicted damage has been repaired. We focus on mammalian cells and their nuclear organization, especially describing the central role of the nucleolus in nuclear stress responses...

Irregularities in nuclear shape and/or alterations to nuclear size are a hallmark of malignancy in a broad range of cancer types. Though these abnormalities are commonly used for diagnostic purposes and are often used to assess cancer progression in the clinic, the mechanisms through which they occur are not well understood. Nuclear size alterations in cancer could potentially arise from aneuploidy, changes in osmotic coupling with the cytoplasm, and perturbations to nucleocytoplasmic transport. Nuclear shape changes may occur due to alterations to cell-generated mechanical stresses and/or alterations to nuclear structural components, which balance those stresses, such as the nuclear lamina and chromatin...