Role In Asymmetric Division Research Articles

Asymmetric T-cell division: insights from cutting-edge experimental techniques and implications for immunotherapy.

Asymmetric cell division is a fundamental process conserved throughout evolution, employed by both prokaryotic and eukaryotic organisms. Its significance lies in its ability to govern cell fate and facilitate the generation of diverse cell types. Therefore, attaining a detailed mechanistic understanding of asymmetric cell division becomes essential for unraveling the complexities of cell fate determination in both healthy and pathological conditions. However, the role of asymmetric division in T-cell biology has only recently been unveiled. Here, we provide an overview of the T-cell asymmetric division field with the particular emphasis on experimental methods and models with the aim to guide the researchers in the selection of appropriate in vitro/in vivo models to study asymmetric division in T cells. We present a comprehensive investigation into the mechanisms governing the asymmetric division in various T-cell subsets underscoring the importance of the asymmetry in fate-determining factor segregation and transcriptional and epigenetic regulation. Furthermore, the intricate interplay of T-cell receptor signaling and the asymmetric division geometry are explored, shedding light on the spatial organization and the impact on cellular fate.

Iterative and Complex Asymmetric Divisions Control Cell Volume Differences in Ciona Notochord Tapering.

The notochord of the invertebrate chordate Ciona forms a tapered rod at tailbud stages consisting of only 40 cylindrical cells in a single-file column. This tapered shape involves differences in notochord cell volume along the anterior-posterior axis. Here,we quantify sibling cell volume asymmetry throughout the developing notochord and find that there are distinctive patterns of unequal cleavage in all 4 bilateral pairs of A-line primary notochord founder cells and also in the B-line-derived secondary notochord founder cells. A quantitative model confirms that the observed patterns of unequal cleavage are sufficient to explain all the anterior-posterior variation in notochord cell volume. Many examples are known of cells that divide asymmetrically to give daughter cells of different size and fate. Here, by contrast, a series of subtle but iterative and finely patterned asymmetric divisions controls the shape of an entire organ. Quantitative 3D analysis of cell shape and spindle positioning allows us to infer multiple cellular mechanisms driving these unequal cleavages, including polarized displacements of the mitotic spindle, contributions from the shape of the mother cell, and late changes occurring between anaphase and abscission that potentially involve differential cortical contractility. We infer differential use of these mechanisms between different notochord blastomeres and also between different rounds of cell division. These results demonstrate a new role for asymmetric division in directly shaping a developing organ and point toward complex underlying mechanisms.

Relationships between Abelson tyrosine kinase (c-abl) and spindle during meiotic division in mouse oocyte in vitro

The c-Abl gene is a nonreceptor tyrosine kinase that has roles in cell growth, control of the cell cycle, initiation of pronuclear movement and actin cytoskeleton dynamics. The present study has examined the localization of c-Abl protein during oocyte activation in mouse in vitro . Confocal immunofluorescence analysis showed that c-Abl originates at the cortex with a crescent shape before the activation and continues up along both sides of the cortex after activation during meiotic division until pronuclear stage. These results demonstrate that c-Abl may play role in asymmetric division of the egg to produce polar body, positioning of the spindle, and may regulate the microtubule cytoskeleton or have some roles in this process.

Neuralized1a regulates asymmetric division in mouse Lewis lung carcinoma cells

Asymmetric division (ASD), the unique characteristic of normal stem cells, is regarded as a stemness marker when applied to the study of cancer stem cells (CSCs). However, the role of ASD in the self-renewal of CSCs and its regulation remain largely unknown. Here, we first established a mouse Lewis lung carcinoma CSC cell line that could undergo asymmetric division (LLC-ASD cells) derived from the parental mouse Lewis lung carcinoma cancer cells (LLC-Parental cells). In vitro assessment of stemness by RT-qPCR and western blot analysis of stem cell markers, clonogenic assay (p < 0.001), single cell spheroid formation assay (p < 0.05) and 96-well-plate single-cell cloning assay (p < 0.01) indicated that the LLC-ASD cells exhibited stronger stemness features in comparison to the LLC-Parental cells. In vivo, tumorigenicity of LLC-ASD cells, transplanted subcutaneously to the nude mice, was increased compared to that of LLC-parental cells (p < 0.05). Further, Neuralized1a, a regulator of ASD in normal stem cells, was highly expressed in the LLC-ASD cells. Silencing Neuralized1a expression in LLC-ASD cells by siRNA weakened the stemness features measured by the in vitro assays listed above (p < 0.05). The tumorigenic ability was also decreased in the nude mice upon Neuralized1a silencing (p < 0.05). Collectively, the present study suggests that Neuralized1a regulates the stemness of LLC-ASD cells which could be the new marker and therapeutic target of CSCs.

Filamin A is required for spindle migration and asymmetric division in mouse oocytes.

Dynamic changes in the actin network are crucial for the cortical migration of spindles and establishment of polarity, to ensure asymmetric division during meiotic maturation. In this study, filamin A (FLNA) was found to be an essential actin regulator that controlled spindle migration and asymmetric division during oocyte meiosis. FLNA was localized in the cytoplasm and enriched at the cortex and near the chromosomes. Knockdown of FLNA impaired meiotic asymmetric division and spindle migration with a decrease in the amount of cytoplasmic actin mesh and cortical actin levels. Moreover, FLNA knockdown reduced the phosphorylation of cofilin and Rho kinase (ROCK) near the spindle. Similar phenotypes, such as decreased filament actin levels, impaired spindle migration and polar body extrusion, were observed when active cofilin (S3A) was overexpressed or ROCK was inhibited. Notably, we found that FLNA and ROCK interacted directly in mouse oocytes. Taken together, our results show that FLNA plays crucial roles in asymmetric division during meiotic maturation by regulating ROCK-cofilin-mediated actin reorganization.-Wang, H., Guo J., Lin, Z., Namgoong, S., Oh, J. S., Kim, N.-H. Filamin A is required for spindle migration and asymmetric division in mouse oocytes.

Small molecule inhibitor of formin homology 2 domains (SMIFH2) reveals the roles of the formin family of proteins in spindle assembly and asymmetric division in mouse oocytes.

Dynamic actin reorganization is the main driving force for spindle migration and asymmetric cell division in mammalian oocytes. It has been reported that various actin nucleators including Formin-2 are involved in the polarization of the spindle and in asymmetric cell division. In mammals, the formin family is comprised of 15 proteins. However, their individual roles in spindle migration and/or asymmetric division have not been elucidated yet. In this study, we employed a newly developed inhibitor for formin family proteins, small molecule inhibitor of formin homology 2 domains (SMIFH2), to assess the functions of the formin family in mouse oocyte maturation. Treatment with SMIFH2 during in vitro maturation of mouse oocytes inhibited maturation by decreasing cytoplasmic and cortical actin levels. In addition, treatment with SMIFH2, especially at higher concentrations (500 μM), impaired the proper formation of meiotic spindles, indicating that formins play a role in meiotic spindle formation. Knockdown of the mDia2 formins caused a similar decrease in oocyte maturation and abnormal spindle morphology, mimicking the phenotype of SMIFH2-treated cells. Collectively, these results suggested that besides Formin-2, the other proteins of the formin, including mDia family play a role in asymmetric division and meiotic spindle formation in mammalian oocytes.

The Par3-like polarity protein Par3L is essential for mammary stem cell maintenance.

The Par polarity proteins play key roles in asymmetric division of Drosophila stem cells; however, whether the same mechanisms control stem cells in mammals is controversial. Although necessary for mammary gland morphogenesis, Par3 is not essential for mammary stem cell function. We discovered that, instead, a previously uncharacterized protein, Par3-Like (Par3L), is vital for mammary gland stem cell maintenance. Par3L function has been mysterious because unlike Par3 it does not interact with atypical protein kinase C or the Par6 polarity protein. We found that Par3L is expressed by multipotent stem cells in the terminal end buds of murine mammary glands. Ablation of Par3L resulted in rapid and profound stem cell loss. Unexpectedly, Par3L, but not Par3, binds to the tumor suppressor protein LKB1 and inhibits its kinase activity. This interaction is key for the function of Par3L in mammary stem cell maintenance. Our data reveal insights into a linkage between cell polarity proteins and stem cell survival, and uncover the first known biological function for Par3L.

Actin-capping proteins play essential roles in asymmetric division of maturing mouse oocytes

Actin polymerization is essential for various stages of mammalian oocyte maturation, including spindle migration, actin cap formation, polar body extrusion and cytokinesis. The heterodimeric actin-capping protein is an essential element of the actin cytoskeleton. It binds to the fast-growing (barbed) ends of actin filaments and plays essential roles in various actin-mediated cellular processes. However, the roles of capping protein in mammalian oocyte maturation are poorly understood. We investigated the roles of capping protein in mouse oocytes and found that it is essential for correct asymmetric spindle migration and polar body extrusion. Capping protein mainly localized in the cytoplasm during maturation. By knocking down or ectopically overexpressing this protein, we revealed that it is crucial for efficient spindle migration and maintenance of the cytoplasmic actin mesh density. Expression of the capping-protein-binding region of CARMIL (also known as LRRC16A) impaired spindle migration and polar body extrusion during oocyte maturation and decreased the density of the cytoplasmic actin mesh. Taken together, these findings show that capping protein is an essential component of the actin cytoskeleton machinery that plays crucial roles in oocyte maturation, presumably by controlling the cytoplasmic actin mesh density.

Explaining the causes of cell death in cyanobacteria: what role for asymmetric division?

Cyanobacteria contribute a significant fraction of global primary production and are therefore of great ecological significance. An individual cyanobacteria cell has four potential fates: to divide, perhaps after a dormant period, to be eaten, to undergo viral lysis, or to undergo cell death. In some studies, cyanobacteria cell death has been classified as programmed cell death, borrowing a concept more widely known in metazoan cells, and there are various biochemical parallels to support such a categorisation. However, at the same time there is a growing awareness of asymmetric division as a fundamental process in bacterial division which can result in non-equal daughter cells with differing fitness. Thanks to recent theoretical and experimental advances it is now possible to explore cyanobacteria cell death in the light of asymmetric division and to test hypotheses on the ultimate causes of cyanobacterial cell death. Assessing the degree of protein damage within individual cells during population growth is a sensible initial research target as is the application of techniques which allow the tracking of cell lineages. The existence of asymmetric division in cyanobacteria is likely given its suggested ubiquity across the bacterial domain of life. It will be technically difficult to test the interaction of asymmetric division with environmental variability, and how that leads to individual cell death via differing susceptibilities to environmental stress. However, testing such ideas could confirm asymmetric division as the ultimate cause of cell death in cyanobacteria and thereby allow a better understanding of the patterns of cell death in natural populations.

Plant Development: Early Events in Lateral Root Initiation

How are the lateral root founder cells specified in the pericycle to initiate lateral root development? An Aux/IAA28 signaling module activates transcription factor GATA23 to control founder cell identity.

Stem cell self-renewal: The role of asymmetric division

Asymmetric division occurs widely in different groups of organisms from single-celled to insects, mammals, and plants. The operation of asymmetrical division may differ widely in different organisms. In multicellular organisms, asymmetrical division is one of the essential features of stem cell biology. The data obtained assume one of the main biological functions of asymmetrical division to be maintenance of cell viability, beginning with stem cells. Cells continuously accumulate toxic inclusions, which are formed by damaged proteins which cannot be degraded by proteasomes. As a result of asymmetric division, these inclusions segregate into one of the daughter cells providing the ability of long-lived proliferation to another cell.

Regulation of asymmetric stem cell division: spindle orientation and the centrosome

Asymmetric stem cell division, as a means of maintaining adequate numbers of stem cells, has attracted widespread attention from researchers in the stem cell biology field. Yet, the molecular and cellular mechanisms that govern asymmetric stem cell division remain poorly understood. Stem cells are not the only cell population that divides asymmetrically, and fortunately, great progress has been made in the understanding of asymmetric cell division during development, providing insight into strategies that stem cells may employ to divide asymmetrically. This review will summarize the importance of stem cell function and the role of asymmetric division in controlling stem cell behavior.

Genetic Dissection of the Sporulation Protein SpoIIE and Its Role in Asymmetric Division inBacillus subtilis

SpoIIE is a dual-function protein in Bacillus subtilis that contributes to the switch from medial to polar cell division during sporulation and is responsible for activating the cell-specific transcription factor sigma(F). SpoIIE consists of an N-terminal domain with 10 membrane-spanning segments (region I), a C-terminal phosphatase domain (region III), and a central domain (region II) of uncertain function. To investigate the role of SpoIIE in polar division, we took advantage of a system for efficiently producing polar septa during growth in a SpoIIE-dependent manner using cells engineered to produce the sporulation protein in response to an inducer. The results show that regions II and III play a critical role in polar septum formation and that specific amino acid substitutions in those regions affect the abilities of SpoIIE both to promote polar division and to localize to the division machinery. Additionally, we show that neither the phosphatase function of SpoIIE nor the N-terminal, membrane-spanning region is needed for the switch to asymmetric division.