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Nature Cell Biology

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https://www.readbyqxmd.com/read/27870831/asymmetric-division-coordinates-collective-cell-migration-in-angiogenesis
#1
Guilherme Costa, Kyle I Harrington, Holly E Lovegrove, Donna J Page, Shilpa Chakravartula, Katie Bentley, Shane P Herbert
The asymmetric division of stem or progenitor cells generates daughters with distinct fates and regulates cell diversity during tissue morphogenesis. However, roles for asymmetric division in other more dynamic morphogenetic processes, such as cell migration, have not previously been described. Here we combine zebrafish in vivo experimental and computational approaches to reveal that heterogeneity introduced by asymmetric division generates multicellular polarity that drives coordinated collective cell migration in angiogenesis...
November 21, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27870828/agonist-stimulated-phosphatidylinositol-3-4-5-trisphosphate-generation-by-scaffolded-phosphoinositide-kinases
#2
Suyong Choi, Andrew C Hedman, Samar Sayedyahossein, Narendra Thapa, David B Sacks, Richard A Anderson
Generation of the lipid messenger phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) is crucial for development, cell growth and survival, and motility, and it becomes dysfunctional in many diseases including cancers. Here we reveal a mechanism for PtdIns(3,4,5)P3 generation by scaffolded phosphoinositide kinases. In this pathway, class I phosphatidylinositol-3-OH kinase (PI(3)K) is assembled by IQGAP1 with PI(4)KIIIα and PIPKIα, which sequentially generate PtdIns(3,4,5)P3 from phosphatidylinositol...
November 21, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27820600/direct-reprogramming-of-fibroblasts-into-renal-tubular-epithelial-cells-by-defined-transcription-factors
#3
Michael M Kaminski, Jelena Tosic, Catena Kresbach, Hannes Engel, Jonas Klockenbusch, Anna-Lena Müller, Roman Pichler, Florian Grahammer, Oliver Kretz, Tobias B Huber, Gerd Walz, Sebastian J Arnold, Soeren S Lienkamp
Direct reprogramming by forced expression of transcription factors can convert one cell type into another. Thus, desired cell types can be generated bypassing pluripotency. However, direct reprogramming towards renal cells remains an unmet challenge. Here, we identify renal cell fate-inducing factors on the basis of their tissue specificity and evolutionarily conserved expression, and demonstrate that combined expression of Emx2, Hnf1b, Hnf4a and Pax8 converts mouse and human fibroblasts into induced renal tubular epithelial cells (iRECs)...
November 7, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27820599/tissue-mechanics-promote-idh1-dependent-hif1%C3%AE-tenascin-c-feedback-to-regulate-glioblastoma%C3%A2-aggression
#4
Yekaterina A Miroshnikova, Janna K Mouw, J Matthew Barnes, Michael W Pickup, Johnathan N Lakins, Youngmi Kim, Khadjia Lobo, Anders I Persson, Gerald F Reis, Tracy R McKnight, Eric C Holland, Joanna J Phillips, Valerie M Weaver
Increased overall survival for patients with glioma brain tumours is associated with mutations in the metabolic regulator isocitrate dehydrogenase 1 (IDH1). Gliomas develop within a mechanically challenged microenvironment that is characterized by a dense extracellular matrix (ECM) that compromises vascular integrity to induce hypoxia and activate HIF1α. We found that glioma aggression and patient prognosis correlate with HIF1α levels and the stiffness of a tenascin C (TNC)-enriched ECM. Gain- and loss-of-function xenograft manipulations demonstrated that a mutant IDH1 restricts glioma aggression by reducing HIF1α-dependent TNC expression to decrease ECM stiffness and mechanosignalling...
November 7, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27798604/lgr6-labels-a-rare-population-of-mammary-gland-progenitor-cells-that-are-able-to-originate-luminal-mammary-tumours
#5
Leander Blaas, Fabio Pucci, Hendrik A Messal, Agneta B Andersson, E Josue Ruiz, Marco Gerling, Iyadh Douagi, Bradley Spencer-Dene, Alexandra Musch, Richard Mitter, Leena Bhaw, Richard Stone, Dorothee Bornhorst, Abdul K Sesay, Jos Jonkers, Gordon Stamp, Ilaria Malanchi, Rune Toftgård, Axel Behrens
The mammary gland is composed of a complex cellular hierarchy with unusual postnatal plasticity. The identities of stem/progenitor cell populations, as well as tumour-initiating cells that give rise to breast cancer, are incompletely understood. Here we show that Lgr6 marks rare populations of cells in both basal and luminal mammary gland compartments in mice. Lineage tracing analysis showed that Lgr6(+) cells are unipotent progenitors, which expand clonally during puberty but diminish in adulthood. In pregnancy or following stimulation with ovarian hormones, adult Lgr6(+) cells regained proliferative potency and their progeny formed alveoli over repeated pregnancies...
October 31, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27992407/lin28-phosphorylation-by-mapk-erk-couples-signalling-to-the-post-transcriptional-control-of%C3%A2-pluripotency
#6
Kaloyan M Tsanov, Daniel S Pearson, Zhaoting Wu, Areum Han, Robinson Triboulet, Marc T Seligson, John T Powers, Jihan K Osborne, Susan Kane, Steven P Gygi, Richard I Gregory, George Q Daley
Signalling and post-transcriptional gene control are both critical for the regulation of pluripotency, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein, has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA biogenesis and direct modulation of mRNA translation. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells, which increases its levels via post-translational stabilization...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27992406/nanoscale-architecture-of-cadherin-based-cell%C3%A2-adhesions
#7
Cristina Bertocchi, Yilin Wang, Andrea Ravasio, Yusuke Hara, Yao Wu, Talgat Sailov, Michelle A Baird, Michael W Davidson, Ronen Zaidel-Bar, Yusuke Toyama, Benoit Ladoux, Rene-Marc Mege, Pakorn Kanchanawong
Multicellularity in animals requires dynamic maintenance of cell-cell contacts. Intercellularly ligated cadherins recruit numerous proteins to form supramolecular complexes that connect with the actin cytoskeleton and support force transmission. However, the molecular organization within such structures remains unknown. Here we mapped protein organization in cadherin-based adhesions by super-resolution microscopy, revealing a multi-compartment nanoscale architecture, with the plasma-membrane-proximal cadherin-catenin compartment segregated from the actin cytoskeletal compartment, bridged by an interface zone containing vinculin...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27992405/tricellular-junctions-regulate-intestinal-stem-cell-behaviour-to-maintain-homeostasis
#8
Martin Resnik-Docampo, Christopher L Koehler, Rebecca I Clark, Joseph M Schinaman, Vivien Sauer, Daniel M Wong, Sophia Lewis, Cecilia D'Alterio, David W Walker, D Leanne Jones
Ageing results in loss of tissue homeostasis across taxa. In the intestine of Drosophila melanogaster, ageing is correlated with an increase in intestinal stem cell (ISC) proliferation, a block in terminal differentiation of progenitor cells, activation of inflammatory pathways, and increased intestinal permeability. However, causal relationships between these phenotypes remain unclear. Here, we demonstrate that ageing results in altered localization and expression of septate junction proteins in the posterior midgut, which is quite pronounced in differentiated enterocytes (ECs) at tricellular junctions (TCJs)...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27918550/selective-y-centromere-inactivation-triggers-chromosome-shattering-in-micronuclei-and-repair-by-non-homologous-end-joining
#9
Peter Ly, Levi S Teitz, Dong H Kim, Ofer Shoshani, Helen Skaletsky, Daniele Fachinetti, David C Page, Don W Cleveland
Chromosome missegregation into a micronucleus can cause complex and localized genomic rearrangements known as chromothripsis, but the underlying mechanisms remain unresolved. Here we developed an inducible Y centromere-selective inactivation strategy by exploiting a CENP-A/histone H3 chimaera to directly examine the fate of missegregated chromosomes in otherwise diploid human cells. Using this approach, we identified a temporal cascade of events that are initiated following centromere inactivation involving chromosome missegregation, fragmentation, and re-ligation that span three consecutive cell cycles...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27918549/a-hypoxia-responsive-traf6-atm-h2ax-signalling-axis-promotes-hif1%C3%AE-activation-tumorigenesis-and%C3%A2-metastasis
#10
Abdol-Hossein Rezaeian, Chien-Feng Li, Ching-Yuan Wu, Xian Zhang, Jorge Delacerda, M James You, Fei Han, Zhen Cai, Yun Seong Jeong, Guoxiang Jin, Liem Phan, Ping-Chieh Chou, Mong-Hong Lee, Mien-Chie Hung, Dos Sarbassov, Hui-Kuan Lin
The understanding of how hypoxia stabilizes and activates HIF1α in the nucleus with related oncogenic signals could revolutionize targeted therapy for cancers. Here, we find that histone H2AX displays oncogenic activity by serving as a crucial regulator of HIF1α signalling. H2AX interacts with HIF1α to prevent its degradation and nuclear export in order to allow successful VHL-independent HIF1α transcriptional activation. We show that mono-ubiquitylation and phosphorylation of H2AX, which are strictly mediated by hypoxia-induced E3 ligase activity of TRAF6 and ATM, critically regulate HIF1α-driven tumorigenesis...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27870830/clonal-fate-mapping-quantifies-the-number-of%C3%A2-haematopoietic-stem-cells-that-arise-during%C3%A2-development
#11
Jonathan Henninger, Buyung Santoso, Stefan Hans, Ellen Durand, Jessica Moore, Christian Mosimann, Michael Brand, David Traver, Leonard Zon
Haematopoietic stem cells (HSCs) arise in the developing aorta during embryogenesis. The number of HSC clones born has been estimated through transplantation, but experimental approaches to assess the absolute number of forming HSCs in a native setting have remained challenging. Here, we applied single-cell and clonal analysis of HSCs in zebrafish to quantify developing HSCs. Targeting creER(T2) in developing cd41:eGFP(+) HSCs enabled long-term assessment of their blood contribution. We also applied the Brainbow-based multicolour Zebrabow system with drl:creER(T2) that is active in early haematopoiesis to induce heritable colour barcoding unique to each HSC and its progeny...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28008184/the-control-of-dna-repair-by-the-cell-cycle
#12
REVIEW
Nicole Hustedt, Daniel Durocher
The correct duplication and transmission of genetic material to daughter cells is the primary objective of the cell division cycle. DNA replication and chromosome segregation present both challenges and opportunities for DNA repair pathways that safeguard genetic information. As a consequence, there is a profound, two-way connection between DNA repair and cell cycle control. Here, we review how DNA repair processes, and DNA double-strand break repair in particular, are regulated during the cell cycle to optimize genomic integrity...
December 23, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/28008183/retraction-g9a-relb-regulates-self-renewal-and-function-of-colon-cancer-initiating-cells-by-silencing-let-7b-and-activating-the-k-ras-%C3%AE-catenin-pathway
#13
Shih-Ting Cha, Ching-Ting Tan, Cheng-Chi Chang, Chia-Yu Chu, Wei-Jiunn Lee, Been-Zen Lin, Ming-Tsan Lin, Min-Liang Kuo
No abstract text is available yet for this article.
December 23, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/28008182/corrigendum-translocon-component-sec62-acts-in-endoplasmic-reticulum-turnover-during-stress-recovery
#14
Fiorenza Fumagalli, Julia Noack, Timothy J Bergmann, Eduardo Cebollero, Giorgia Brambilla Pisoni, Elisa Fasana, Ilaria Fregno, Carmela Galli, Marisa Loi, Tatiana Soldà, Rocco D'Antuono, Andrea Raimondi, Martin Jung, Armin Melnyk, Stefan Schorr, Anne Schreiber, Luca Simonelli, Luca Varani, Caroline Wilson-Zbinden, Oliver Zerbe, Kay Hofmann, Matthias Peter, Manfredo Quadroni, Richard Zimmermann, Maurizio Molinari
No abstract text is available yet for this article.
December 23, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/28008181/haematopoietic-stem-cells-show-their-true-colours
#15
Trista E North, Wolfram Goessling
Delineating the behaviour of haematopoietic stem cells (HSCs) in vivo has thus far proven challenging. Two studies in zebrafish and mouse models now track HSCs in vivo using fate mapping with multicolour approaches to provide further insights into clonal events that regulate blood development, HSC function and differentiation during homeostasis and stress conditions.
December 23, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/28008180/y-chromothripsis
#16
Emily M Hatch
Micronucleation of missegregated chromatin can lead to substantial chromosome rearrangements via chromothripsis. However, the molecular details of micronucleus-based chromothripsis are still unclear. Now, an elegant system that specifically induces missegregation of the Y chromosome provides insight into this process, including a role for non-homologous end joining.
December 23, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/28008179/resolving-the-cadherin-f-actin-connection
#17
Mitchell K L Han, Johan de Rooij
Cadherin adhesion complexes have recently emerged as sensors of tissue tension that regulate key developmental processes. Super-resolution microscopy experiments now unravel the spatial organization of the interface between cadherins and the actin cytoskeleton and reveal how vinculin, a central component in cadherin mechanotransduction, is regulated by mechanical and biochemical signals.
December 23, 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27897157/getting-a-grip-on-collective-cell-migration
#18
Tamal Das, Joachim P Spatz
Many cell types in our body move in a collective manner, which requires individual cells to align their movements relative to that of their neighbours. A mechanism is now described in which cadherin-rich protrusions are extended from leading migrating cells and engulfed by follower cells to guide collective migration.
December 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27870829/crumbs2-promotes-cell-ingression-during-the-epithelial-to-mesenchymal-transition-at-gastrulation
#19
Nitya Ramkumar, Tatiana Omelchenko, Nancy F Silva-Gagliardi, C Jane McGlade, Jan Wijnholds, Kathryn V Anderson
During gastrulation of the mouse embryo, individual cells ingress in an apparently stochastic pattern during the epithelial-to-mesenchymal transition (EMT). Here we define a critical role of the apical protein Crumbs2 (CRB2) in the gastrulation EMT. Static and live imaging show that ingressing cells in Crumbs2 mutant embryos become trapped at the primitive streak, where they continue to express the epiblast transcription factor SOX2 and retain thin E-cadherin-containing connections to the epiblast surface that trap them at the streak...
December 2016: Nature Cell Biology
https://www.readbyqxmd.com/read/27842058/developmentally-programmed-germ-cell-remodelling-by-endodermal-cell-cannibalism
#20
Yusuff Abdu, Chelsea Maniscalco, John M Heddleston, Teng-Leong Chew, Jeremy Nance
Primordial germ cells (PGCs) in many species associate intimately with endodermal cells, but the significance of such interactions is largely unexplored. Here, we show that Caenorhabditis elegans PGCs form lobes that are removed and digested by endodermal cells, dramatically altering PGC size and mitochondrial content. We demonstrate that endodermal cells do not scavenge lobes PGCs shed, but rather, actively remove lobes from the cell body. CED-10 (Rac)-induced actin, DYN-1 (dynamin) and LST-4 (SNX9) transiently surround lobe necks and are required within endodermal cells for lobe scission, suggesting that scission occurs through a mechanism resembling vesicle endocytosis...
December 2016: Nature Cell Biology
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