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asymmetric cell division

Claire Levrier, Martin C Sadowski, Anja Rockstroh, Brian Gabrielli, Maria Kavallaris, Melanie Lehman, Rohan A Davis, Colleen C Nelson
The lack of a cure for metastatic castrate-resistant prostate cancer (mCRPC) highlights the urgent need for more efficient drugs to fight this disease. Here, we report the mechanism of action of the natural product 6α-acetoxyanopterine (6-AA) in prostate cancer cells. At low nanomolar doses, this potent cytotoxic alkaloid from the Australian endemic tree Anopterus macleayanus induced a strong accumulation of LNCaP and PC-3 (prostate cancer) cells as well as HeLa (cervical cancer) cells in mitosis, severe mitotic spindle defects and asymmetric cell divisions, ultimately leading to mitotic catastrophe accompanied by cell death through apoptosis...
October 19, 2016: Molecular Cancer Therapeutics
Ying Zhang, Xiaoyu Guo, Juan Dong
Cell polarization is commonly used for the regulation of stem cell asymmetric division in both animals and plants. Stomatal development in Arabidopsis, a process that produces breathing pores in the epidermis, requires asymmetric cell division to differentiate highly specialized guard cells while maintaining a stem cell population [1, 2]. The BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL) protein exhibits a polarized localization pattern in the cell and is required for differential cell fates resulting from asymmetric cell division [3]...
October 5, 2016: Current Biology: CB
Mayu Inaba, Yukiko M Yamashita
Asymmetric cell division (ACD) is utilized in many stem cell systems to produce two daughter cells with different cell fates. Despite the fundamental importance of ACD during development and tissue homeostasis, the nature of ACD is far from being fully understood. Step-by-step observation of events during ACD allows us to understand processes that lead to ACD. Here we describe examples of how we evaluate ACD in vivo using the Drosophila male germline stem cell system.
2017: Methods in Molecular Biology
Cher-Pheng Ooi, Sarah Schuster, Christelle Cren-Travaillé, Eloise Bertiaux, Alain Cosson, Sophie Goyard, Sylvie Perrot, Brice Rotureau
Trypanosoma vivax is the most prevalent trypanosome species in African cattle. It is thought to be transmitted by tsetse flies after cyclical development restricted to the vector mouthparts. Here, we investigated the kinetics of T. vivax development in Glossina morsitans morsitans by serial dissections over 1 week to reveal differentiation and proliferation stages. After 3 days, stable numbers of attached epimastigotes were seen proliferating by symmetric division in the cibarium and proboscis, consistent with colonization and maintenance of a parasite population for the remaining lifespan of the tsetse fly...
2016: Frontiers in Cellular and Infection Microbiology
Valerie C Coffman, Matthew B A McDermott, Blerta Shtylla, Adriana T Dawes
Positioning of microtubule organizing centers (MTOCs) incorporates biochemical and mechanical cues for proper alignment of the mitotic spindle and cell division site. Current experimental and theoretical studies in the early C. elegans embryo assume remarkable changes in the origin and polarity of forces acting on the MTOCs. These changes must occur over a few minutes, between initial centration and rotation of the pronuclear complex and entry into mitosis, and the models do not replicate in vivo timing of centration and rotation...
October 12, 2016: Molecular Biology of the Cell
Fumio Arai
Hematopoietic stem cells (HSCs) are characterized by their ability to self-renew and differentiate into all blood lineage cells. The fate decisions of HSCs (self-renewal versus differentiation) are made through the process of cell division and are often compared to "birth" and "death". Stem cells give rise to undifferentiated stem cells (birth) or differentiate into progenitor cells (death). This process is regulated by asymmetric/symmetric divisions of HSCs. It has been proposed that fate determination occurs as a stochastic process and that individual stem cell dynamics are randomly regulated...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Darcie L Moore, Sebastian Jessberger
Accumulating evidence suggests that mammalian cells asymmetrically segregate cellular components ranging from genomic DNA to organelles and damaged proteins during cell division. Asymmetric inheritance upon mammalian cell division may be specifically important to ensure cellular fitness and propagate cellular potency to individual progeny, for example in the context of somatic stem cell division. We review here recent advances in the field and discuss potential effects and underlying mechanisms that mediate asymmetric segregation of cellular components during mammalian cell division...
October 4, 2016: Trends in Cell Biology
Alys M Cheatle Jarvela, Kristen A Yankura, Veronica F Hinman
How neural stem cells generate the correct number and type of differentiated neurons in appropriate places is an important question in developmental biology. Although nervous systems are diverse across phyla, many taxa have a larva that forms an anterior concentration of serotonergic neurons, or apical organ. The number of neurons in these organs is highly variable. Previous work demonstrated that the sea star embryo initially has a pan-neurogenic ectoderm, but the genetic mechanism that directs only a subset of these cells to generate serotonergic neurons in a particular location had not been resolved...
October 5, 2016: Development
Christopher J Sifuentes, Jung-Woong Kim, Anand Swaroop, Pamela A Raymond
Purpose: Zebrafish neurons regenerate from Müller glia following retinal lesions. Genes and signaling pathways important for retinal regeneration in zebrafish have been described, but our understanding of how Müller glial stem cell properties are regulated is incomplete. Mammalian Müller glia possess a latent neurogenic capacity that might be enhanced in regenerative therapies to treat degenerative retinal diseases. Methods: To identify transcriptional changes associated with stem cell properties in zebrafish Müller glia, we performed a comparative transcriptome analysis from isolated cells at 8 and 16 hours following an acute photic lesion, prior to the asymmetric division that produces retinal progenitors...
October 1, 2016: Investigative Ophthalmology & Visual Science
Si-Jing Song, Qiao-Chu Wang, Ru-Xia Jia, Xiang-Shun Cui, Nam-Hyung Kim, Shao-Chen Sun
Mammalian oocyte asymmetric division relies on the eccentric positioning of the spindle, resulting in the polar body formation. Small signaling G protein Rac1 is a member of GTPases, which regulates a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. However, effects of Rac1 on the porcine oocyte maturation and early embryo development are not fully understood. In present study we investigated the role of Rac1 in oocyte maturation and embryo cleavage...
October 3, 2016: Scientific Reports
Ranhua Xiong, Freya Joris, Sayuan Liang, Riet De Rycke, Saskia Lippens, Jo Demeester, Andre Skirtach, Koen Raemdonck, Uwe Himmelreich, Stefaan C De Smedt, Kevin Braeckmans
Long-term in vivo imaging of cells is crucial for the understanding of cellular fate in biological processes in cancer research, immunology, or in cell-based therapies such as beta cell transplantation in type I diabetes or stem cell therapy. Traditionally, cell labeling with the desired contrast agent occurs ex vivo via spontaneous endocytosis, which is a variable and slow process that requires optimization for each particular label-cell type combination. Following endocytic uptake, the contrast agents mostly remain entrapped in the endolysosomal compartment, which leads to signal instability, cytotoxicity, and asymmetric inheritance of the labels upon cell division...
October 3, 2016: Nano Letters
Gustav van Niekerk, Lester M Davids, Suzèl M Hattingh, Anna-Mart Engelbrecht
The cancer stem cell (CSC) model has emerged as a prominent paradigm for explaining tumour heterogeneity. CSCs in tumour recurrence and drug resistance have also been implicated in a number of studies. In fact, CSCs are often identified by their expression of drug-efflux proteins which are also highly expressed in normal stem cells. Similarly, pro-survival or proliferation signalling often exhibited by stem cells is regularly reported as being upregulated by CSC. Here we review evidence suggesting that many aspects of CSCs are more readily described by clonal evolution...
September 27, 2016: International Journal of Cancer. Journal International du Cancer
Malgorzata J Liro, Lesilee S Rose
Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types a cortically localized complex consisting of Gα, GPR-1/2, and LIN-5 (Gαi/Pins/Mud, Gαi/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle...
September 26, 2016: Genetics
Kei Sakamoto
Notch signaling is involved in cell-cell communication. It is an evolutionarily ancient mechanism and plays a fundamental role in development. The typical function of Notch signaling is the regulation of cell fate segregation at asymmetric division; however, a role in tumorigenesis has also been suggested. Inactivating mutations of NOTCH1 are present in about 10 % of cases of squamous cell carcinoma of the skin, oral cavity, esophagus, and lung, rendering it one of the most frequently mutated genes in squamous cell carcinoma...
September 26, 2016: Pathology International
Jing Zhao, Meng-Xiang Sun
In angiosperm, asymmetric zygote division is critical for embryogenesis. The molecular mechanism underlying this process has gained a great attention recently. Some players involve in the control of both accurate position and correct orientation of zygote division plane have been found, which provide useful clues for the extensive investigations. It is getting clear that both internal and external factors are involved in this complex regulatory mechanism and the asymmetric zygote division seems with great impact in cell fate determination and embryo pattern formation...
September 23, 2016: Plant Signaling & Behavior
Lihua Wang, Pengcheng Bu, Xiling Shen
miR-34a-mediated asymmetric cell division reins in excessive stem cell expansion during tissue regeneration in the intestine and colon. Loss of miR-34a switches asymmetric division to symmetric division and enhances stem cell proliferation. Asymmetric division also occurs in the early stages of colon cancer stem cells. Mechanistically, miR-34a, Numb, and Notch form a feed-forward loop that specifies cell fate when stem cells divide.
July 2016: Molecular & Cellular Oncology
Dante P Ricci, Michael D Melfi, Keren Lasker, David L Dill, Harley H McAdams, Lucy Shapiro
Faithful cell cycle progression in the dimorphic bacterium Caulobacter crescentus requires spatiotemporal regulation of gene expression and cell pole differentiation. We discovered an essential DNA-associated protein, GapR, that is required for Caulobacter growth and asymmetric division. GapR interacts with adenine and thymine (AT)-rich chromosomal loci, associates with the promoter regions of cell cycle-regulated genes, and shares hundreds of recognition sites in common with known master regulators of cell cycle-dependent gene expression...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jinwei Zhu, Yuan Shang, Yitian Xia, Rongguang Zhang, Mingjie Zhang
The membrane-associated guanylate kinase (MAGUK) scaffold proteins share a signature guanylate kinase (GK) domain. Despite their diverse functional roles in cell polarity control and synaptic signaling, the currently known mode of action of MAGUK GK is via its binding to phosphorylated short peptides from target proteins. Here, we discover that the GK domain of DLG MAGUK binds to an unphosphorylated and autonomously folded domain within the stalk region (MAGUK binding stalk [MBS] domain) of a kinesin motor KIF13B with high specificity and affinity...
September 15, 2016: Structure
Stephen B Keysar, Phuong N Le, Bettina Miller, Brian C Jackson, Justin R Eagles, Cera Nieto, Jihye Kim, Binwu Tang, Magdalena J Glogowska, J Jason Morton, Nuria Padilla-Just, Karina Gomez, Emily Warnock, Julie Reisinger, John J Arcaroli, Wells A Messersmith, Lalage M Wakefield, Dexiang Gao, Aik-Choon Tan, Hilary Serracino, Antonio Jimeno
BACKGROUND: We have an incomplete understanding of the differences between cancer stem cells (CSCs) in human papillomavirus-positive (HPV-positive) and -negative (HPV-negative) head and neck squamous cell cancer (HNSCC). The PI3K pathway has the most frequent activating genetic events in HNSCC (especially HPV-positive driven), but the differential signaling between CSCs and non-CSCs is also unknown. METHODS: We addressed these unresolved questions using CSCs identified from 10 HNSCC patient-derived xenografts (PDXs)...
January 2017: Journal of the National Cancer Institute
Benjamin Peters, Jonathan Casey, Jack Aidley, Stuart Zohrab, Michael Borg, David Twell, Lynette Brownfield
The development of the male germline within pollen relies upon the activation of numerous target genes by the transcription factor DUO POLLEN1 (DUO1). The expression of DUO1 is restricted to the male germline and is first detected shortly after the asymmetric division that segregates the germ cell lineage. Transcriptional regulation is critical in controlling DUO1 expression since transcriptional and translational fusions show similar expression patterns. Here we identify key promoter sequences required for the germline-specific regulation of DUO1 transcription...
September 13, 2016: Plant Physiology
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