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Nature Cell Biology

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https://www.readbyqxmd.com/read/28530660/endoglin-prevents-vascular-malformation-by-regulating-flow-induced-cell-migration-and-specification-through-vegfr2-signalling
#1
Yi Jin, Lars Muhl, Mikhail Burmakin, Yixin Wang, Anne-Claire Duchez, Christer Betsholtz, Helen M Arthur, Lars Jakobsson
Loss-of-function (LOF) mutations in the endothelial cell (EC)-enriched gene endoglin (ENG) cause the human disease hereditary haemorrhagic telangiectasia-1, characterized by vascular malformations promoted by vascular endothelial growth factor A (VEGFA). How ENG deficiency alters EC behaviour to trigger these anomalies is not understood. Mosaic ENG deletion in the postnatal mouse rendered Eng LOF ECs insensitive to flow-mediated venous to arterial migration. Eng LOF ECs retained within arterioles acquired venous characteristics and secondary ENG-independent proliferation resulting in arteriovenous malformation (AVM)...
May 22, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28530659/actin-cortex-architecture-regulates-cell-surface-tension
#2
Priyamvada Chugh, Andrew G Clark, Matthew B Smith, Davide A D Cassani, Kai Dierkes, Anan Ragab, Philippe P Roux, Guillaume Charras, Guillaume Salbreux, Ewa K Paluch
Animal cell shape is largely determined by the cortex, a thin actin network underlying the plasma membrane in which myosin-driven stresses generate contractile tension. Tension gradients result in local contractions and drive cell deformations. Previous cortical tension regulation studies have focused on myosin motors. Here, we show that cortical actin network architecture is equally important. First, we observe that actin cortex thickness and tension are inversely correlated during cell-cycle progression. We then show that the actin filament length regulators CFL1, CAPZB and DIAPH1 regulate mitotic cortex thickness and find that both increasing and decreasing thickness decreases tension in mitosis...
May 22, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28530658/endoglin-controls-blood-vessel-diameter-through-endothelial-cell-shape-changes-in-response-to-haemodynamic-cues
#3
Wade W Sugden, Robert Meissner, Tinri Aegerter-Wilmsen, Roman Tsaryk, Elvin V Leonard, Jeroen Bussmann, Mailin J Hamm, Wiebke Herzog, Yi Jin, Lars Jakobsson, Cornelia Denz, Arndt F Siekmann
The hierarchical organization of properly sized blood vessels ensures the correct distribution of blood to all organs of the body, and is controlled via haemodynamic cues. In current concepts, an endothelium-dependent shear stress set point causes blood vessel enlargement in response to higher flow rates, while lower flow would lead to blood vessel narrowing, thereby establishing homeostasis. We show that during zebrafish embryonic development increases in flow, after an initial expansion of blood vessel diameters, eventually lead to vessel contraction...
May 22, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28530657/normal-and-cancerous-mammary-stem-cells-evade-interferon-induced-constraint-through-the-mir-199a-lcor-axis
#4
Toni Celià-Terrassa, Daniel D Liu, Abrar Choudhury, Xiang Hang, Yong Wei, Jose Zamalloa, Raymundo Alfaro-Aco, Rumela Chakrabarti, Yi-Zhou Jiang, Bong Ihn Koh, Heath A Smith, Christina DeCoste, Jun-Jing Li, Zhi-Ming Shao, Yibin Kang
Tumour-initiating cells, or cancer stem cells (CSCs), possess stem-cell-like properties observed in normal adult tissue stem cells. Normal and cancerous stem cells may therefore share regulatory mechanisms for maintaining self-renewing capacity and resisting differentiation elicited by cell-intrinsic or microenvironmental cues. Here, we show that miR-199a promotes stem cell properties in mammary stem cells and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses...
May 22, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28504708/receptor-oligomerization-guides-pathway-choice-between-proteasomal-and-autophagic-degradation
#5
Kefeng Lu, Fabian den Brave, Stefan Jentsch
Abnormal or aggregated proteins have a strong cytotoxic potential and are causative for human disorders such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. If not restored by molecular chaperones, abnormal proteins are typically degraded by proteasomes or eliminated by selective autophagy. The discovery that both pathways are initiated by substrate ubiquitylation but utilize different ubiquitin receptors incited a debate over how pathway choice is achieved. Here, we demonstrate in yeast that pathway choice is made after substrate ubiquitylation by competing ubiquitin receptors harbouring either proteasome- or autophagy-related protein 8 (Atg8/LC3)-binding modules...
May 15, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28504707/regulation-of-mitochondrial-biogenesis-in-erythropoiesis-by-mtorc1-mediated-protein%C3%A2-translation
#6
Xin Liu, Yuannyu Zhang, Min Ni, Hui Cao, Robert A J Signer, Dan Li, Mushan Li, Zhimin Gu, Zeping Hu, Kathryn E Dickerson, Samuel E Weinberg, Navdeep S Chandel, Ralph J DeBerardinis, Feng Zhou, Zhen Shao, Jian Xu
Advances in genomic profiling present new challenges of explaining how changes in DNA and RNA are translated into proteins linking genotype to phenotype. Here we compare the genome-scale proteomic and transcriptomic changes in human primary haematopoietic stem/progenitor cells and erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are selectively regulated through protein translation during erythroid specification...
May 15, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28504706/the-mitochondrial-respiratory-chain-is-essential-for-haematopoietic-stem-cell-function
#7
Elena Ansó, Samuel E Weinberg, Lauren P Diebold, Benjamin J Thompson, Sébastien Malinge, Paul T Schumacker, Xin Liu, Yuannyu Zhang, Zhen Shao, Mya Steadman, Kelly M Marsh, Jian Xu, John D Crispino, Navdeep S Chandel
Adult and fetal haematopoietic stem cells (HSCs) display a glycolytic phenotype, which is required for maintenance of stemness; however, whether mitochondrial respiration is required to maintain HSC function is not known. Here we report that loss of the mitochondrial complex III subunit Rieske iron-sulfur protein (RISP) in fetal mouse HSCs allows them to proliferate but impairs their differentiation, resulting in anaemia and prenatal death. RISP-null fetal HSCs displayed impaired respiration resulting in a decreased NAD(+)/NADH ratio...
May 15, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28504705/wounding-induces-dedifferentiation-of-epidermal-gata6-cells-and-acquisition-of-stem-cell-properties
#8
Giacomo Donati, Emanuel Rognoni, Toru Hiratsuka, Kifayathullah Liakath-Ali, Esther Hoste, Gozde Kar, Melis Kayikci, Roslin Russell, Kai Kretzschmar, Klaas W Mulder, Sarah A Teichmann, Fiona M Watt
The epidermis is maintained by multiple stem cell populations whose progeny differentiate along diverse, and spatially distinct, lineages. Here we show that the transcription factor Gata6 controls the identity of the previously uncharacterized sebaceous duct (SD) lineage and identify the Gata6 downstream transcription factor network that specifies a lineage switch between sebocytes and SD cells. During wound healing differentiated Gata6(+) cells migrate from the SD into the interfollicular epidermis and dedifferentiate, acquiring the ability to undergo long-term self-renewal and differentiate into a much wider range of epidermal lineages than in undamaged tissue...
May 15, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28481328/leptin-receptor-expressing-bone-marrow-stromal-cells-are-myofibroblasts-in-primary-myelofibrosis
#9
Matthew Decker, Leticia Martinez-Morentin, Guannan Wang, Yeojin Lee, Qingxue Liu, Juliana Leslie, Lei Ding
Bone marrow fibrosis is a critical component of primary myelofibrosis (PMF). However, the origin of the myofibroblasts that drive fibrosis is unknown. Using genetic fate mapping we found that bone marrow leptin receptor (Lepr)-expressing mesenchymal stromal lineage cells expanded extensively and were the fibrogenic cells in PMF. These stromal cells downregulated the expression of key haematopoietic-stem-cell-supporting factors and upregulated genes associated with fibrosis and osteogenesis, indicating fibrogenic conversion...
May 8, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28459443/regulated-ire1-dependent-mrna-decay-sets-the-threshold-for-dendritic-cell-survival
#10
Simon J Tavernier, Fabiola Osorio, Lana Vandersarren, Jessica Vetters, Nele Vanlangenakker, Gert Van Isterdael, Karl Vergote, Riet De Rycke, Eef Parthoens, Lianne van de Laar, Takao Iwawaki, Juan R Del Valle, Chih-Chi Andrew Hu, Bart N Lambrecht, Sophie Janssens
The IRE1-XBP1 signalling pathway is part of a cellular programme that protects against endoplasmic reticulum (ER) stress, but also controls development and survival of immune cells. Loss of XBP1 in splenic type 1 conventional dendritic cells (cDC1s) results in functional alterations without affecting cell survival. However, in mucosal cDC1s, loss of XBP1 impaired survival in a tissue-specific manner-while lung cDC1s die, intestinal cDC1s survive. This was not caused by differential activation of ER stress cell-death regulators CHOP or JNK...
May 1, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28446817/shh-mediated-centrosomal-recruitment-of-pka-promotes-symmetric-proliferative-neuroepithelial-cell%C3%A2-division
#11
Murielle Saade, Elena Gonzalez-Gobartt, Rene Escalona, Susana Usieto, Elisa Martí
Tight control of the balance between self-expanding symmetric and self-renewing asymmetric neural progenitor divisions is crucial to regulate the number of cells in the developing central nervous system. We recently demonstrated that Sonic hedgehog (Shh) signalling is required for the expansion of motor neuron progenitors by maintaining symmetric divisions. Here we show that activation of Shh/Gli signalling in dividing neuroepithelial cells controls the symmetric recruitment of PKA to the centrosomes that nucleate the mitotic spindle, maintaining symmetric proliferative divisions...
April 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28346438/basolateral-protrusion-and-apical-contraction-cooperatively-drive-drosophila-germ-band-extension
#12
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
#13
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/28288130/parl-mediates-smac-proteolytic-maturation-in-mitochondria-to-promote-apoptosis
#14
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
#15
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
#16
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/28436968/metabolic-control-of-primed-human-pluripotent-stem-cell-fate-and-function-by-the-mir-200c-sirt2-axis
#17
Young Cha, Min-Joon Han, Hyuk-Jin Cha, Janet Zoldan, Alison Burkart, Jin Hyuk Jung, Yongwoo Jang, Chun-Hyung Kim, Ho-Chang Jeong, Byung-Gyu Kim, Robert Langer, C Ronald Kahn, Leonard Guarente, Kwang-Soo Kim
A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the 'Warburg effect', which is also observed in primed human pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28436967/microtubule-minus-end-regulation-at-spindle-poles-by-an-aspm-katanin-complex
#18
Kai Jiang, Lenka Rezabkova, Shasha Hua, Qingyang Liu, Guido Capitani, A F Maarten Altelaar, Albert J R Heck, Richard A Kammerer, Michel O Steinmetz, Anna Akhmanova
ASPM (known as Asp in fly and ASPM-1 in worm) is a microcephaly-associated protein family that regulates spindle architecture, but the underlying mechanism is poorly understood. Here, we show that ASPM forms a complex with another protein linked to microcephaly, the microtubule-severing ATPase katanin. ASPM and katanin localize to spindle poles in a mutually dependent manner and regulate spindle flux. X-ray crystallography revealed that the heterodimer formed by the N- and C-terminal domains of the katanin subunits p60 and p80, respectively, binds conserved motifs in ASPM...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28436966/microbial-metabolites-regulate-host-lipid-metabolism-through-nr5a-hedgehog-signalling
#19
Chih-Chun Janet Lin, Meng C Wang
Microorganisms and their hosts share the same environment, and microbial metabolic molecules (metabolites) exert crucial effects on host physiology. Environmental factors not only shape the composition of the host's resident microorganisms, but also modulate their metabolism. However, the exact molecular relationship among the environment, microbial metabolites and host metabolism remains largely unknown. Here, we discovered that environmental methionine tunes bacterial methyl metabolism to regulate host mitochondrial dynamics and lipid metabolism in Caenorhabditis elegans through an endocrine crosstalk involving NR5A nuclear receptor and Hedgehog signalling...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28436965/a-three-dimensional-model-of-human-lung-development-and-disease-from-pluripotent-stem-cells
#20
Ya-Wen Chen, Sarah Xuelian Huang, Ana Luisa Rodrigues Toste de Carvalho, Siu-Hong Ho, Mohammad Naimul Islam, Stefano Volpi, Luigi D Notarangelo, Michael Ciancanelli, Jean-Laurent Casanova, Jahar Bhattacharya, Alice F Liang, Laura M Palermo, Matteo Porotto, Anne Moscona, Hans-Willem Snoeck
Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation...
May 2017: Nature Cell Biology
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