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asymmetric cell division

Amy Reilein, David Melamed, Simon Tavaré, Daniel Kalderon
Cancer-initiating gatekeeper mutations that arise in stem cells would be especially potent if they stabilize and expand an affected stem cell lineage. It is therefore important to understand how different stem cell organization strategies promote or prevent variant stem cell amplification in response to different types of mutation, including those that activate proliferation. Stem cell numbers can be maintained constant while producing differentiated products through individually asymmetrical division outcomes or by population asymmetry strategies in which individual stem cell lineages necessarily compete for niche space...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Arun Kumar, Priyanka Sharma, Mercè Gomar-Alba, Zhanna Shcheprova, Anne Daulny, Trinidad Sanmartín, Irene Matucci, Charlotta Funaya, Miguel Beato, Manuel Mendoza
The acquisition of cellular identity is coupled to changes in the nuclear periphery and nuclear pore complexes (NPCs). Whether and how these changes determine cell fate remain unclear. We have uncovered a mechanism that regulates NPC acetylation to direct cell fate after asymmetric division in budding yeast. The lysine deacetylase Hos3 associates specifically with daughter cell NPCs during mitosis to delay cell cycle entry (Start). Hos3-dependent deacetylation of nuclear basket and central channel nucleoporins establishes daughter-cell-specific nuclear accumulation of the transcriptional repressor Whi5 during anaphase and perinuclear silencing of the G1/S cyclin gene CLN2 in the following G1 phase...
March 12, 2018: Nature Cell Biology
Joanna Hołówka, Damian Trojanowski, Mateusz Janczak, Dagmara Jakimowicz, Jolanta Zakrzewska-Czerwińska
The bacterial chromosome undergoes dynamic changes in response to ongoing cellular processes and adaptation to environmental conditions. Among the many proteins involved in maintaining this dynamism, the most abundant is the nucleoid-associated protein (NAP), HU. In mycobacteria, the HU homolog, HupB, possesses an additional C-terminal domain that resembles that of eukaryotic histones H1/H5. Recently, we demonstrated that the highly abundant HupB occupies the entirety of the M. smegmatis chromosome and exhibits a bias from the origin ( oriC ) to the terminus ( ter )...
March 12, 2018: Journal of Bacteriology
Simone Culurgioni, Sara Mari, Paola Bonetti, Sara Gallini, Greta Bonetto, Martha Brennich, Adam Round, Francesco Nicassio, Marina Mapelli
Asymmetric cell divisions balance stem cell proliferation and differentiation to sustain tissue morphogenesis and homeostasis. During asymmetric divisions, fate determinants and niche contacts segregate unequally between daughters, but little is known on how this is achieved mechanistically. In Drosophila neuroblasts and murine mammary stem cells, the association of the spindle orientation protein LGN with the stem cell adaptor Inscuteable has been connected to asymmetry. Here we report the crystal structure of Drosophila LGN in complex with the asymmetric domain of Inscuteable, which reveals a tetrameric arrangement of intertwined molecules...
March 9, 2018: Nature Communications
Sun K Kim, Siwei Zhang, Michael E Werner, Eva J Brotslaw, Jennifer W Mitchell, Mohamed M Altabbaa, Brian J Mitchell
Most epithelial cells polarize along the axis of the tissue, a feature known as planar cell polarity (PCP). The initiation of PCP requires cell-cell signaling via the noncanonical Wnt/PCP pathway. Additionally, changes in the cytoskeleton both facilitate and reflect this polarity. We have identified CLAMP/Spef1 as a novel regulator of PCP signaling. In addition to decorating microtubules (MTs) and the ciliary rootlet, a pool of CLAMP localizes at the apical cell cortex. Depletion of CLAMP leads to the loss of PCP protein asymmetry, defects in cilia polarity, and defects in the angle of cell division...
March 7, 2018: Journal of Cell Biology
Delphine Duteil, Yves Tourette, Adrien Eberlin, Dominica Willmann, Dharmeshkumar Patel, Nikolaus Friedrichs, Judith M Müller, Roland Schüle
Nir/ Noc2l is an inhibitor of histone acetyl-transferases (INHAT). In addition to its function on histone acetylation, Nir binds to p53 and TAp63 to regulate their activity. Here, we show that epidermis-specific ablation of Nir impairs epidermal stratification and barrier function, thereby causing perinatal lethality. Nir-deficient epidermis lacks appendages and remains single layered during embryogenesis. Cell proliferation is inhibited, whereas apoptosis and p53 acetylation is increased, indicating that Nir is controlling cell proliferation by limiting p53 acetylation...
February 28, 2018: Development
Chwee Tat Koe, Ye Sing Tan, Max Lönnfors, Seong Kwon Hur, Christine Siok Lan Low, Yingjie Zhang, Pakorn Kanchanawong, Vytas A Bankaitis, Hongyan Wang
A central feature of most stem cells is the ability to self-renew and undergo differentiation via asymmetric division. However, during asymmetric division the role of phosphatidylinositol (PI) lipids and their regulators is not well established. Here, we show that the sole type I PI transfer protein, Vibrator, controls asymmetric division of Drosophila neural stem cells (NSCs) by physically anchoring myosin II regulatory light chain, Sqh, to the NSC cortex. Depletion of vib or disruption of its lipid binding and transfer activities disrupts NSC polarity...
February 27, 2018: ELife
Huijing Du, Yangyang Wang, Daniel Haensel, Briana Lee, Xing Dai, Qing Nie
The mammalian skin epidermis is a stratified epithelium composed of multiple layers of epithelial cells that exist in appropriate sizes and proportions, and with distinct boundaries separating each other. How the epidermis develops from a single layer of committed precursor cells to form a complex multilayered structure of multiple cell types remains elusive. Here, we construct stochastic, three-dimensional, and multiscale models consisting of a lineage of multiple cell types to study the control of epidermal development...
February 26, 2018: PLoS Computational Biology
Deepak Saini, Yojiro Yamanaka
During the first few days in the mouse preimplantation embryo, two types of cells, polar and apolar cells are generated from spherical totipotent blastomeres. Sequential morphogenetic events, polarization, compaction, and asymmetric division, are essential for the generation of the first distinct cell populations, polar and apolar cells, which establish the outer/inner configuration within the embryo. This leads to position-dependent activation of the Hippo signaling pathway and lineage-specific gene expression to form the trophectoderm and inner cell mass in a blastocyst...
2018: Current Topics in Developmental Biology
Marissa Renardy, Alexandra Jilkine, Leili Shahriyari, Ching-Shan Chou
Multicellular tissues are continually turning over, and homeostasis is maintained through regulated proliferation and differentiation of stem cells and progenitors. Following tissue injury, a dramatic increase in cell proliferation is commonly observed, resulting in rapid restoration of tissue size. This regulation is thought to occur via multiple feedback loops acting on cell self-renewal or differentiation. Models of ordinary differential equations have been widely used to study the cell lineage system. Prior modeling studies have suggested that loss of homeostasis and initiation of tumorigenesis can be contributed to the loss of control of these processes, and the rate of symmetric versus asymmetric division of the stem cells may also be altered...
February 19, 2018: Journal of Theoretical Biology
Veronica F Hinman, Robert D Burke
The phylogenetic position of echinoderms is well suited to revealing shared features of deuterostomes that distinguish them from other bilaterians. Although echinoderm neurobiology remains understudied, genomic resources, molecular methods, and systems approaches have enabled progress in understanding mechanisms of embryonic neurogenesis. Even though the morphology of echinoderm larvae is diverse, larval nervous systems, which arise during gastrulation, have numerous similarities in their organization. Diverse neural subtypes and specialized sensory neurons have been identified and details of neuroanatomy using neuron-specific labels provide hypotheses for neural function...
February 22, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
Zelin Shan, Yuting Tu, Ying Yang, Ziheng Liu, Menglong Zeng, Huisha Xu, Jiafu Long, Mingjie Zhang, Yu Cai, Wenyu Wen
Uneven distribution and local concentration of protein complexes on distinct membrane cortices is a fundamental property in numerous biological processes, including Drosophila neuroblast (NB) asymmetric cell divisions and cell polarity in general. In NBs, the cell fate determinant Numb forms a basal crescent together with Pon and is segregated into the basal daughter cell to initiate its differentiation. Here we discover that Numb PTB domain, using two distinct binding surfaces, recognizes repeating motifs within Pon in a previously unrecognized mode...
February 21, 2018: Nature Communications
Olga A Mineyeva, Grigori Enikolopov, Alexei A Koulakov
The modes of stem cell divisions (e.g., symmetric vs. asymmetric) can have a profound impact on the number of progeny and tissue growth, repair, and function. This is particularly relevant for adult neural stem cells, since stem cell-derived neurons affect cognitive and mental states, resistance to stress and disease, and response to therapies. Here we show that although dividing stem cells in the adult hippocampus display a certain bias towards paired distribution (which could imply the prevalence of symmetric divisions), this bias already exists in the distribution of the general population of stem cells and may be responsible for the perceived occurrence of symmetric stem cell divisions...
February 21, 2018: Scientific Reports
Annika K Weimer, Juliana L Matos, Nidhi Sharma, Farah Patell, James A H Murray, Walter Dewitte, Dominique C Bergmann
Plants, with cells fixed in place by rigid walls, often utilize spatial and temporally distinct cell division programs to organize and maintain organs. This leads to the question of how developmental regulators interact with the cell cycle machinery to link cell division events with particular developmental trajectories. In Arabidopsis leaves, the development of stomata, 2-celled epidermal valves that mediate plant-atmosphere gas exchange, relies on a series of oriented stem-cell-like asymmetric divisions followed by a single symmetric division...
February 21, 2018: Development
Ana García Del Arco, Bruce A Edgar, Sylvia Erhardt
Stem cells of the Drosophila midgut (ISCs) are the only mitotically dividing cells of the epithelium and, therefore, presumably the only epithelial cells that require functional kinetochores for microtubule spindle attachment during mitosis. The histone variant CENP-A marks centromeric chromatin as the site of kinetochore formation and spindle attachment during mitotic chromosome segregation. Here, we show that centromeric proteins distribute asymmetrically during ISC division. Whereas newly synthesized CENP-A is enriched in differentiating progeny, CENP-C is undetectable in these cells...
February 20, 2018: Cell Reports
Nash Delta Rochman, Dan M Popescu, Sean Sun
Many single-cell observables are highly heterogeneous. A part of this heterogeneity stems from
 age-related phenomena: the fact that there is a nonuniform distribution of cells with different ages.
 This has led to a renewed interest in analytic methodologies including use of the "von Foerster
 equation" for predicting population growth and cell age distributions. Here we discuss how some of
 the most popular implementations of this machinery assume a strong condition on the ergodicity of
 the cell cycle duration ensemble...
February 20, 2018: Physical Biology
Ronald A Backer, Pleun Hombrink, Christina Helbig, Derk Amsen
CD8+ T cells clear primary infections with intracellular pathogens and provide long-term immunity against reinfection. Two different types of CD8+ T cells are responsible for these functions: short-lived effector T cells and memory T cells. The cellular relationship between these two types of CD8+ T cells has been subject to much investigation. Both cell types can derive from a single naïve CD8+ T cell precursor. Their generation requires a fate choice early during a T cell response. As a result, two populations of T cells emerge...
2018: Advances in Immunology
Siddharth Deshpande, Willem Kasper Spoelstra, Marleen van Doorn, Jacob Kerssemakers, Cees Dekker
Liposomes, self-assembled vesicles with a lipid-bilayer boundary similar to cell membranes, are extensively used in both fundamental and applied sciences. Manipulation of their physical properties, such as growth and division, may significantly expand their use as model systems in cellular and synthetic biology. Several approaches have been explored to controllably divide liposomes, such as shape transformation through temperature cycling, incorporation of additional lipids, and the encapsulation of protein division machinery...
February 18, 2018: ACS Nano
Lachlan Harris, Oressia Zalucki, Michael Piper
Measuring the mean duration of synthesis-phase (T s ) and of the total cell-cycle (T c ) within progenitor cell populations can provide important insights into the biology governing these cells. Rather than a passive process that shows little variability across cellular contexts, the cell-cycle is instead highly regulated. For example, in the rodent forebrain, T s is selectively lengthened in radial glial progenitor cells undergoing symmetric versus asymmetric division. This lengthening is thought to minimize the potential for copying errors that can occur during DNA replication...
February 14, 2018: Journal of Molecular Histology
Gregor-Alexander Pilz, Sara Bottes, Marion Betizeau, David J Jörg, Stefano Carta, Benjamin D Simons, Fritjof Helmchen, Sebastian Jessberger
Neural stem and progenitor cells (NSPCs) generate neurons throughout life in the mammalian hippocampus. We used chronic in vivo imaging and followed genetically labeled individual NSPCs and their progeny in the mouse hippocampus for up to 2 months. We show that NSPCs targeted by the endogenous Achaete-scute homolog 1 (Ascl1) promoter undergo limited rounds of symmetric and asymmetric divisions, eliciting a burst of neurogenic activity, after which they are lost. Further, our data reveal unexpected asymmetric divisions of nonradial glia-like NSPCs...
February 9, 2018: Science
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