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Nature Cell Biology

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https://www.readbyqxmd.com/read/28422952/when-cancer-needs-what-s-non-essential
#1
Mark R Sullivan, Matthew G Vander Heiden
The non-essential amino acids serine and glycine are critical for proliferative metabolism. A study in Nature now finds that dietary serine and glycine deprivation inhibits growth of some tumours. Whether this dietary intervention is effective depends on both the oncogenic context and tumour tissue of origin.
April 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28414315/the-emt-activator-zeb1-is-a-key-factor-for-cell-plasticity-and-promotes-metastasis-in-pancreatic-cancer
#2
Angela M Krebs, Julia Mitschke, María Lasierra Losada, Otto Schmalhofer, Melanie Boerries, Hauke Busch, Martin Boettcher, Dimitrios Mougiakakos, Wilfried Reichardt, Peter Bronsert, Valerie G Brunton, Christian Pilarsky, Thomas H Winkler, Simone Brabletz, Marc P Stemmler, Thomas Brabletz
Metastasis is the major cause of cancer-associated death. Partial activation of the epithelial-to-mesenchymal transition program (partial EMT) was considered a major driver of tumour progression from initiation to metastasis. However, the role of EMT in promoting metastasis has recently been challenged, in particular concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in pancreatic cancer. In contrast, we show here that in the same pancreatic cancer model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model), the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion and notably metastasis...
April 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28414314/cell-competition-with-normal-epithelial-cells-promotes-apical-extrusion-of-transformed-cells-through-metabolic%C3%A2-changes
#3
Shunsuke Kon, Kojiro Ishibashi, Hiroto Katoh, Sho Kitamoto, Takanobu Shirai, Shinya Tanaka, Mihoko Kajita, Susumu Ishikawa, Hajime Yamauchi, Yuta Yako, Tomoko Kamasaki, Tomohiro Matsumoto, Hirotaka Watanabe, Riku Egami, Ayana Sasaki, Atsuko Nishikawa, Ikumi Kameda, Takeshi Maruyama, Rika Narumi, Tomoko Morita, Yoshiteru Sasaki, Ryosuke Enoki, Sato Honma, Hiromi Imamura, Masanobu Oshima, Tomoyoshi Soga, Jun-Ichi Miyazaki, Michael R Duchen, Jin-Min Nam, Yasuhito Onodera, Shingo Yoshioka, Junichi Kikuta, Masaru Ishii, Masamichi Imajo, Eisuke Nishida, Yoichiro Fujioka, Yusuke Ohba, Toshiro Sato, Yasuyuki Fujita
Recent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells. In addition, glucose uptake is elevated, leading to higher lactate production. The mitochondrial dysfunction is driven by upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively regulates elimination of RasV12-transformed cells...
April 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28414313/alternative-direct-stem-cell-derivatives-defined-by-stem-cell-location-and-graded-wnt-signalling
#4
Amy Reilein, David Melamed, Karen Sophia Park, Ari Berg, Elisa Cimetta, Nina Tandon, Gordana Vunjak-Novakovic, Sarah Finkelstein, Daniel Kalderon
Adult stem cells provide a renewable source of differentiated cells for a wide variety of tissues and generally give rise to multiple cell types. Basic principles of stem cell organization and regulation underlying this behaviour are emerging. Local niche signals maintain stem cells, while different sets of signals act outside the niche to diversify initially equivalent stem cell progeny. Here we show that Drosophila ovarian follicle stem cells (FSCs) produced two distinct cell types directly. This cell fate choice was determined by the anterior-posterior position of an FSC and by the magnitude of spatially graded Wnt pathway activity...
April 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28414312/high-resolution-myogenic-lineage-mapping-by-single-cell-mass-cytometry
#5
Ermelinda Porpiglia, Nikolay Samusik, Andrew Tri Van Ho, Benjamin D Cosgrove, Thach Mai, Kara L Davis, Astraea Jager, Garry P Nolan, Sean C Bendall, Wendy J Fantl, Helen M Blau
Muscle regeneration is a dynamic process during which cell state and identity change over time. A major roadblock has been a lack of tools to resolve a myogenic progression in vivo. Here we capitalize on a transformative technology, single-cell mass cytometry (CyTOF), to identify in vivo skeletal muscle stem cell and previously unrecognized progenitor populations that precede differentiation. We discovered two cell surface markers, CD9 and CD104, whose combined expression enabled in vivo identification and prospective isolation of stem and progenitor cells...
April 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28394884/long-term-hormone-responsive-organoid-cultures-of-human-endometrium-in-a-chemically-defined-medium
#6
Margherita Y Turco, Lucy Gardner, Jasmine Hughes, Tereza Cindrova-Davies, Maria J Gomez, Lydia Farrell, Michael Hollinshead, Steven G E Marsh, Jan J Brosens, Hilary O Critchley, Benjamin D Simons, Myriam Hemberger, Bon-Kyoung Koo, Ashley Moffett, Graham J Burton
In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and pregnancy. Despite the importance of the endometrium as the site of implantation and nutritional support for the conceptus, there are no long-term culture systems that recapitulate endometrial function in vitro. We adapted conditions used to establish human adult stem-cell-derived organoid cultures to generate three-dimensional cultures of normal and decidualized human endometrium. These organoids expand long-term, are genetically stable and differentiate following treatment with reproductive hormones...
April 10, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28394883/pdgf-signalling-guides-neural-crest-contribution-to-the-haematopoietic-stem-cell-specification-niche
#7
Erich W Damm, Wilson K Clements
Haematopoietic stem cells (HSCs) support maintenance of the haematopoietic and immune systems throughout the life of vertebrates, and are the therapeutic component of bone marrow transplants. Understanding native specification of HSCs, to uncover key signals that might help improve in vitro directed differentiation protocols, has been a long-standing biomedical goal. The current impossibility of specifying true HSCs in vitro suggests that key signals remain unknown. We speculated that such signals might be presented by surrounding 'niche' cells, but no such cells have been defined...
April 10, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28368372/ercc1-xpf-cooperates-with-ctcf-and-cohesin-to%C3%A2-facilitate-the-developmental-silencing-of-imprinted%C3%A2-genes
#8
Georgia Chatzinikolaou, Zivkos Apostolou, Tamara Aid-Pavlidis, Anna Ioannidou, Ismene Karakasilioti, Giorgio L Papadopoulos, Michalis Aivaliotis, Maria Tsekrekou, John Strouboulis, Theodore Kosteas, George A Garinis
Inborn defects in DNA repair are associated with complex developmental disorders whose causal mechanisms are poorly understood. Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development...
April 3, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28368371/cul-2-lrr-1-and-ubxn-3-drive-replisome-disassembly-during-dna-replication-termination-and%C3%A2-mitosis
#9
Remi Sonneville, Sara Priego Moreno, Axel Knebel, Clare Johnson, C James Hastie, Anton Gartner, Agnieszka Gambus, Karim Labib
Replisome disassembly is the final step of DNA replication in eukaryotes, involving the ubiquitylation and CDC48-dependent dissolution of the CMG helicase (CDC45-MCM-GINS). Using Caenorhabditis elegans early embryos and Xenopus laevis egg extracts, we show that the E3 ligase CUL-2(LRR-1) associates with the replisome and drives ubiquitylation and disassembly of CMG, together with the CDC-48 cofactors UFD-1 and NPL-4. Removal of CMG from chromatin in frog egg extracts requires CUL2 neddylation, and our data identify chromatin recruitment of CUL2(LRR1) as a key regulated step during DNA replication termination...
April 3, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346438/basolateral-protrusion-and-apical-contraction-cooperatively-drive-drosophila-germ-band-extension
#10
Zijun Sun, Christopher Amourda, Murat Shagirov, Yusuke Hara, Timothy E Saunders, Yusuke Toyama
Throughout development, tissues undergo complex morphological changes, resulting from cellular mechanics that evolve over time and in three-dimensional space. During Drosophila germ-band extension (GBE), cell intercalation is the key mechanism for tissue extension, and the associated apical junction remodelling is driven by polarized myosin-II-dependent contraction. However, the contribution of the basolateral cellular mechanics to GBE remains poorly understood. Here, we characterize how cells coordinate their shape from the apical to the basal side during rosette formation, a hallmark of cell intercalation...
March 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346437/friction-forces-position-the-neural-anlage
#11
Michael Smutny, Zsuzsa Ákos, Silvia Grigolon, Shayan Shamipour, Verena Ruprecht, Daniel Čapek, Martin Behrndt, Ekaterina Papusheva, Masazumi Tada, Björn Hof, Tamás Vicsek, Guillaume Salbreux, Carl-Philipp Heisenberg
During embryonic development, mechanical forces are essential for cellular rearrangements driving tissue morphogenesis. Here, we show that in the early zebrafish embryo, friction forces are generated at the interface between anterior axial mesoderm (prechordal plate, ppl) progenitors migrating towards the animal pole and neurectoderm progenitors moving in the opposite direction towards the vegetal pole of the embryo. These friction forces lead to global rearrangement of cells within the neurectoderm and determine the position of the neural anlage...
March 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28319093/human-haematopoietic-stem-cell-lineage-commitment-is-a-continuous-process
#12
Lars Velten, Simon F Haas, Simon Raffel, Sandra Blaszkiewicz, Saiful Islam, Bianca P Hennig, Christoph Hirche, Christoph Lutz, Eike C Buss, Daniel Nowak, Tobias Boch, Wolf-Karsten Hofmann, Anthony D Ho, Wolfgang Huber, Andreas Trumpp, Marieke A G Essers, Lars M Steinmetz
Blood formation is believed to occur through stepwise progression of haematopoietic stem cells (HSCs) following a tree-like hierarchy of oligo-, bi- and unipotent progenitors. However, this model is based on the analysis of predefined flow-sorted cell populations. Here we integrated flow cytometric, transcriptomic and functional data at single-cell resolution to quantitatively map early differentiation of human HSCs towards lineage commitment. During homeostasis, individual HSCs gradually acquire lineage biases along multiple directions without passing through discrete hierarchically organized progenitor populations...
March 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28288130/parl-mediates-smac-proteolytic-maturation-in-mitochondria-to-promote-apoptosis
#13
Shotaro Saita, Hendrik Nolte, Kai Uwe Fiedler, Hamid Kashkar, A Saskia Venne, René P Zahedi, Marcus Krüger, Thomas Langer
Mitochondria drive apoptosis by releasing pro-apoptotic proteins that promote caspase activation in the cytosol. The rhomboid protease PARL, an intramembrane cleaving peptidase in the inner membrane, regulates mitophagy and plays an ill-defined role in apoptosis. Here, we employed PARL-based proteomics to define its substrate spectrum. Our data identified the mitochondrial pro-apoptotic protein Smac (also known as DIABLO) as a PARL substrate. In apoptotic cells, Smac is released into the cytosol and promotes caspase activity by inhibiting inhibitors of apoptosis (IAPs)...
March 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28288129/endoplasmic-reticulum-mediated-microtubule-alignment-governs-cytoplasmic-streaming
#14
Kenji Kimura, Alexandre Mamane, Tohru Sasaki, Kohta Sato, Jun Takagi, Ritsuya Niwayama, Lars Hufnagel, Yuta Shimamoto, Jean-François Joanny, Seiichi Uchida, Akatsuki Kimura
Cytoplasmic streaming refers to a collective movement of cytoplasm observed in many cell types. The mechanism of meiotic cytoplasmic streaming (MeiCS) in Caenorhabditis elegans zygotes is puzzling as the direction of the flow is not predefined by cell polarity and occasionally reverses. Here, we demonstrate that the endoplasmic reticulum (ER) network structure is required for the collective flow. Using a combination of RNAi, microscopy and image processing of C. elegans zygotes, we devise a theoretical model, which reproduces and predicts the emergence and reversal of the flow...
March 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28248302/tissue-scale-coordination-of-cellular-behaviour-promotes-epidermal-wound-repair-in-live-mice
#15
Sangbum Park, David G Gonzalez, Boris Guirao, Jonathan D Boucher, Katie Cockburn, Edward D Marsh, Kailin R Mesa, Samara Brown, Panteleimon Rompolas, Ann M Haberman, Yohanns Bellaïche, Valentina Greco
Tissue repair is fundamental to our survival as tissues are challenged by recurrent damage. During mammalian skin repair, cells respond by migrating and proliferating to close the wound. However, the coordination of cellular repair behaviours and their effects on homeostatic functions in a live mammal remains unclear. Here we capture the spatiotemporal dynamics of individual epithelial behaviours by imaging wound re-epithelialization in live mice. Differentiated cells migrate while the rate of differentiation changes depending on local rate of migration and tissue architecture...
March 1, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28218910/a-mechanically-active-heterotypic-e-cadherin-n-cadherin-adhesion-enables-fibroblasts-to%C3%A2-drive-cancer-cell-invasion
#16
Anna Labernadie, Takuya Kato, Agustí Brugués, Xavier Serra-Picamal, Stefanie Derzsi, Esther Arwert, Anne Weston, Victor González-Tarragó, Alberto Elosegui-Artola, Lorenzo Albertazzi, Jordi Alcaraz, Pere Roca-Cusachs, Erik Sahai, Xavier Trepat
Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. This adhesion is mechanically active; when subjected to force it triggers β-catenin recruitment and adhesion reinforcement dependent on α-catenin/vinculin interaction. Impairment of E-cadherin/N-cadherin adhesion abrogates the ability of CAFs to guide collective cell migration and blocks cancer cell invasion...
February 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28192422/identification-of-quiescent-and-spatially-restricted-mammary-stem-cells-that-are-hormone-responsive
#17
Nai Yang Fu, Anne C Rios, Bhupinder Pal, Charity W Law, Paul Jamieson, Ruijie Liu, François Vaillant, Felicity Jackling, Kevin He Liu, Gordon K Smyth, Geoffrey J Lindeman, Matthew E Ritchie, Jane E Visvader
Despite accumulating evidence for a mammary differentiation hierarchy, the basal compartment comprising stem cells remains poorly characterized. Through gene expression profiling of Lgr5(+) basal epithelial cells, we identify a new marker, Tetraspanin8 (Tspan8). Fractionation based on Tspan8 and Lgr5 expression uncovered three distinct mammary stem cell (MaSC) subsets in the adult mammary gland. These exist in a largely quiescent state but differ in their reconstituting ability, spatial localization, and their molecular and epigenetic signatures...
February 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346441/altering-the-threshold-of-an-excitable-signal-transduction-network-changes-cell-migratory-modes
#18
Yuchuan Miao, Sayak Bhattacharya, Marc Edwards, Huaqing Cai, Takanari Inoue, Pablo A Iglesias, Peter N Devreotes
The diverse migratory modes displayed by different cell types are generally believed to be idiosyncratic. Here we show that the migratory behaviour of Dictyostelium was switched from amoeboid to keratocyte-like and oscillatory modes by synthetically decreasing phosphatidylinositol-4,5-bisphosphate levels or increasing Ras/Rap-related activities. The perturbations at these key nodes of an excitable signal transduction network initiated a causal chain of events: the threshold for network activation was lowered, the speed and range of propagating waves of signal transduction activity increased, actin-driven cellular protrusions expanded and, consequently, the cell migratory mode transitions ensued...
April 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346440/endocytic-proteins-are-partitioned-at-the-edge-of-the-clathrin-lattice-in-mammalian-cells
#19
Kem A Sochacki, Andrea M Dickey, Marie-Paule Strub, Justin W Taraska
Dozens of proteins capture, polymerize and reshape the clathrin lattice during clathrin-mediated endocytosis (CME). How or if this ensemble of proteins is organized in relation to the clathrin coat is unknown. Here, we map key molecules involved in CME at the nanoscale using correlative super-resolution light and transmission electron microscopy. We localize 19 different endocytic proteins (amphiphysin1, AP2, β2-arrestin, CALM, clathrin, DAB2, dynamin2, EPS15, epsin1, epsin2, FCHO2, HIP1R, intersectin, NECAP, SNX9, stonin2, syndapin2, transferrin receptor, VAMP2) on thousands of individual clathrin structures, generating a comprehensive molecular architecture of endocytosis with nanoscale precision...
April 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346439/hippo-signalling-governs-cytosolic-nucleic-acid-sensing-through-yap-taz-mediated-tbk1-blockade
#20
Qian Zhang, Fansen Meng, Shasha Chen, Steven W Plouffe, Shiying Wu, Shengduo Liu, Xinran Li, Ruyuan Zhou, Junxian Wang, Bin Zhao, Jianming Liu, Jun Qin, Jian Zou, Xin-Hua Feng, Kun-Liang Guan, Pinglong Xu
The Hippo pathway senses cellular conditions and regulates YAP/TAZ to control cellular and tissue homeostasis, while TBK1 is central for cytosolic nucleic acid sensing and antiviral defence. The correlation between cellular nutrient/physical status and host antiviral defence is interesting but not well understood. Here we find that YAP/TAZ act as natural inhibitors of TBK1 and are vital for antiviral physiology. Independent of transcriptional regulation and through the transactivation domain, YAP/TAZ associate directly with TBK1 and abolish virus-induced TBK1 activation, by preventing TBK1 Lys63-linked ubiquitylation and the binding of adaptors/substrates...
April 2017: Nature Cell Biology
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