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Nature Cell Biology

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https://www.readbyqxmd.com/read/28319093/human-haematopoietic-stem-cell-lineage-commitment-is-a-continuous-process
#1
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/28319092/the-tdh-gcn5l1-fbxo15-kbp-axis-limits-mitochondrial-biogenesis-in-mouse-embryonic-stem%C3%A2-cells
#2
Valerio Donato, Massimo Bonora, Daniele Simoneschi, Davide Sartini, Yasusei Kudo, Anita Saraf, Laurence Florens, Michael P Washburn, Matthias Stadtfeld, Paolo Pinton, Michele Pagano
Self-renewing naive mouse embryonic stem cells (mESCs) contain few mitochondria, which increase in number and volume at the onset of differentiation. KBP (encoded by Kif1bp) is an interactor of the mitochondrial-associated kinesin Kif1Bα. We found that TDH, responsible for mitochondrial production of acetyl-CoA in mESCs, and the acetyltransferase GCN5L1 cooperate to acetylate Lys501 in KBP, allowing its recognition by and degradation via Fbxo15, an F-box protein transcriptionally controlled by the pluripotency core factors and repressed following differentiation...
March 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28288130/parl-mediates-smac-proteolytic-maturation-in-mitochondria-to-promote-apoptosis
#3
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
#4
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/28263958/genomic-instability-during-reprogramming-by-nuclear-transfer-is-dna-replication-dependent
#5
Gloryn Chia, Judith Agudo, Nathan Treff, Mark V Sauer, David Billing, Brian D Brown, Richard Baer, Dieter Egli
Somatic cells can be reprogrammed to a pluripotent state by nuclear transfer into oocytes, yet developmental arrest often occurs. While incomplete transcriptional reprogramming is known to cause developmental failure, reprogramming also involves concurrent changes in cell cycle progression and nuclear structure. Here we study cellular reprogramming events in human and mouse nuclear transfer embryos prior to embryonic genome activation. We show that genetic instability marked by frequent chromosome segregation errors and DNA damage arise prior to, and independent of, transcriptional activity...
March 6, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28263957/the-tetrameric-kinesin-kif25-suppresses-pre-mitotic-centrosome-separation-to-establish-proper-spindle%C3%A2-orientation
#6
Justin Decarreau, Michael Wagenbach, Eric Lynch, Aaron R Halpern, Joshua C Vaughan, Justin Kollman, Linda Wordeman
Microtubules tether centrosomes together during interphase. How this is accomplished and what benefit it provides to the cell is not known. We have identified a bipolar, minus-end-directed kinesin, Kif25, that suppresses centrosome separation. Kif25 is required to prevent premature centrosome separation during interphase. We show that premature centrosome separation leads to microtubule-dependent nuclear translocation, culminating in eccentric nuclear positioning that disrupts the cortical spindle positioning machinery...
March 6, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28263956/shank-proteins-limit-integrin-activation-by-directly-interacting-with-rap1-and%C3%A2-r-ras
#7
Johanna Lilja, Thomas Zacharchenko, Maria Georgiadou, Guillaume Jacquemet, Nicola De Franceschi, Emilia Peuhu, Hellyeh Hamidi, Jeroen Pouwels, Victoria Martens, Fatemeh Hassani Nia, Malte Beifuss, Tobias Boeckers, Hans-Juergen Kreienkamp, Igor L Barsukov, Johanna Ivaska
SHANK3, a synaptic scaffold protein and actin regulator, is widely expressed outside of the central nervous system with predominantly unknown function. Solving the structure of the SHANK3 N-terminal region revealed that the SPN domain is an unexpected Ras-association domain with high affinity for GTP-bound Ras and Rap G-proteins. The role of Rap1 in integrin activation is well established but the mechanisms to antagonize it remain largely unknown. Here, we show that SHANK1 and SHANK3 act as integrin activation inhibitors by sequestering active Rap1 and R-Ras via the SPN domain and thus limiting their bioavailability at the plasma membrane...
March 6, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28248302/tissue-scale-coordination-of-cellular-behaviour-promotes-epidermal-wound-repair-in-live-mice
#8
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/28250419/tubulin-acetylation-protects-long-lived-microtubules-against-mechanical-ageing
#9
Didier Portran, Laura Schaedel, Zhenjie Xu, Manuel Théry, Maxence V Nachury
Long-lived microtubules endow the eukaryotic cell with long-range transport abilities. While long-lived microtubules are acetylated on Lys40 of α-tubulin (αK40), acetylation takes place after stabilization and does not protect against depolymerization. Instead, αK40 acetylation has been proposed to mechanically stabilize microtubules. Yet how modification of αK40, a residue exposed to the microtubule lumen and inaccessible to microtubule-associated proteins and motors, could affect microtubule mechanics remains an open question...
February 27, 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
#10
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/28218908/cell-matrix-signals-specify-bone-endothelial-cells-during-developmental-osteogenesis
#11
Urs H Langen, Mara E Pitulescu, Jung Mo Kim, Rocio Enriquez-Gasca, Kishor K Sivaraj, Anjali P Kusumbe, Amit Singh, Jacopo Di Russo, M Gabriele Bixel, Bin Zhou, Lydia Sorokin, Juan M Vaquerizas, Ralf H Adams
Blood vessels in the mammalian skeletal system control bone formation and support haematopoiesis by generating local niche environments. While a specialized capillary subtype, termed type H, has been recently shown to couple angiogenesis and osteogenesis in adolescent, adult and ageing mice, little is known about the formation of specific endothelial cell populations during early developmental endochondral bone formation. Here, we report that embryonic and early postnatal long bone contains a specialized endothelial cell subtype, termed type E, which strongly supports osteoblast lineage cells and later gives rise to other endothelial cell subpopulations...
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
#12
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/28192421/g1-cyclins-link-proliferation-pluripotency-and-differentiation-of-embryonic-stem-cells
#13
Lijun Liu, Wojciech Michowski, Hiroyuki Inuzuka, Kouhei Shimizu, Naoe Taira Nihira, Joel M Chick, Na Li, Yan Geng, Alice Y Meng, Alban Ordureau, Aleksandra Kołodziejczyk, Keith L Ligon, Roderick T Bronson, Kornelia Polyak, J Wade Harper, Steven P Gygi, Wenyi Wei, Piotr Sicinski
Progression of mammalian cells through the G1 and S phases of the cell cycle is driven by the D-type and E-type cyclins. According to the current models, at least one of these cyclin families must be present to allow cell proliferation. Here, we show that several cell types can proliferate in the absence of all G1 cyclins. However, following ablation of G1 cyclins, embryonic stem (ES) cells attenuated their pluripotent characteristics, with the majority of cells acquiring the trophectodermal cell fate. We established that G1 cyclins, together with their associated cyclin-dependent kinases (CDKs), phosphorylate and stabilize the core pluripotency factors Nanog, Sox2 and Oct4...
February 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28248308/pulling-cells-out-of-tumours
#14
Andrew J Ewald
Tumours are highly complex and contain multiple cell types. Cancer-associated fibroblasts are now shown to have a critical role in directly leading cancer cell invasion. This intercellular interaction relies on a mechanically active cadherin-based junction, and CAF-led invasion is demonstrated to require E-cadherin in the cancer cell.
March 1, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28248307/twist-of-fate-for-skeletal-muscle-mesenchymal-cells
#15
Natalya A Goloviznina, Michael Kyba
Skeletal muscles are composed of different types of fibres. Can these be thought of as distinct lineages with specific lineage-restricted progenitors? A provocative study now proposes that mesenchymal cells expressing the transcription factor Twist2 act as myogenic progenitors with selective type IIb fibre-differentiation potential.
March 1, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28248306/erratum-long-range-self-organization-of-cytoskeletal-myosin-ii-filament-stacks
#16
Shiqiong Hu, Kinjal Dasbiswas, Zhenhuan Guo, Yee-Han Tee, Visalatchi Thiagarajan, Pascal Hersen, Teng-Leong Chew, Samuel A Safran, Ronen Zaidel-Bar, Alexander D Bershadsky
No abstract text is available yet for this article.
March 1, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28248305/inheritance-of-protection-from-osmotic-stress
#17
Kiyomi R Kaneshiro, Susan Strome
Exposure of mother worms to mild osmotic stress induces gene expression changes in offspring that protect them from strong osmotic stress. Inheritance of protection is now shown to depend on altered insulin-like signalling in the maternal germline, which confers protection through increased expression of zygotic gpdh-2, a rate-limiting enzyme in glycerol biosynthesis.
March 1, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28248304/the-scientist-citizen-time-to-become-political
#18
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
March 1, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28248303/g1-cyclins-protect-pluripotency
#19
Julia Arand, Julien Sage
G1 cyclins are considered essential for DNA replication and cell division. A recent report now shows that some cells can cycle in the absence of G1 cyclins. In embryonic stem cells and cancer cells, G1 cyclins are required to activate cyclin-dependent kinases to phosphorylate core pluripotency factors and maintain pluripotency.
March 1, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28218909/a-twist2-dependent-progenitor-cell-contributes-to-adult-skeletal-muscle
#20
Ning Liu, Glynnis A Garry, Stephen Li, Svetlana Bezprozvannaya, Efrain Sanchez-Ortiz, Beibei Chen, John M Shelton, Priscilla Jaichander, Rhonda Bassel-Duby, Eric N Olson
Skeletal muscle possesses remarkable regenerative potential due to satellite cells, an injury-responsive stem cell population located beneath the muscle basal lamina that expresses Pax7. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a myogenic lineage that resides outside the basal lamina of adult skeletal muscle. Tw2(+) progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro, and can fuse with themselves and with satellite cells...
March 2017: Nature Cell Biology
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