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Nature Cell Biology

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https://www.readbyqxmd.com/read/29335530/segregation-of-mitochondrial-dna-heteroplasmy-through-a-developmental-genetic-bottleneck-in-human-embryos
#1
Vasileios I Floros, Angela Pyle, Sabine Dietmann, Wei Wei, Walfred W C Tang, Naoko Irie, Brendan Payne, Antonio Capalbo, Laila Noli, Jonathan Coxhead, Gavin Hudson, Moira Crosier, Henrik Strahl, Yacoub Khalaf, Mitinori Saitou, Dusko Ilic, M Azim Surani, Patrick F Chinnery
Mitochondrial DNA (mtDNA) mutations cause inherited diseases and are implicated in the pathogenesis of common late-onset disorders, but how they arise is not clear1,2. Here we show that mtDNA mutations are present in primordial germ cells (PGCs) within healthy female human embryos. Isolated PGCs have a profound reduction in mtDNA content, with discrete mitochondria containing ~5 mtDNA molecules. Single-cell deep mtDNA sequencing of in vivo human female PGCs showed rare variants reaching higher heteroplasmy levels in late PGCs, consistent with the observed genetic bottleneck...
January 15, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29335529/transient-scute-activation-via-a-self-stimulatory-loop-directs-enteroendocrine-cell-pair-specification-from-self-renewing-intestinal-stem-cells
#2
Jun Chen, Na Xu, Chenhui Wang, Pin Huang, Huanwei Huang, Zhen Jin, Zhongsheng Yu, Tao Cai, Renjie Jiao, Rongwen Xi
The process through which multiple types of cell-lineage-restricted progenitor cells are specified from multipotent stem cells is unclear. Here we show that, in intestinal stem cell lineages in adult Drosophila, in which the Delta-Notch-signalling-guided progenitor cell differentiation into enterocytes is the default mode, the specification of enteroendocrine cells (EEs) is initiated by transient Scute activation in a process driven by transcriptional self-stimulation combined with a negative feedback regulation between Scute and Notch targets...
January 15, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29335528/exd2-governs-germ-stem-cell-homeostasis-and-lifespan-by-promoting-mitoribosome-integrity-and-translation
#3
Joana Silva, Suvi Aivio, Philip A Knobel, Laura J Bailey, Andreu Casali, Maria Vinaixa, Isabel Garcia-Cao, Étienne Coyaud, Alexis A Jourdain, Pablo Pérez-Ferreros, Ana M Rojas, Albert Antolin-Fontes, Sara Samino-Gené, Brian Raught, Acaimo González-Reyes, Lluís Ribas de Pouplana, Aidan J Doherty, Oscar Yanes, Travis H Stracker
Mitochondria are subcellular organelles that are critical for meeting the bioenergetic and biosynthetic needs of the cell. Mitochondrial function relies on genes and RNA species encoded both in the nucleus and mitochondria, and on their coordinated translation, import and respiratory complex assembly. Here, we characterize EXD2 (exonuclease 3'-5' domain-containing 2), a nuclear-encoded gene, and show that it is targeted to the mitochondria and prevents the aberrant association of messenger RNAs with the mitochondrial ribosome...
January 15, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29335527/myosin-va-is-required-for-preciliary-vesicle-transportation-to-the-mother-centriole-during-ciliogenesis
#4
Chien-Ting Wu, Hsin-Yi Chen, Tang K Tang
Primary cilia play essential roles in signal transduction and development. The docking of preciliary vesicles at the distal appendages of a mother centriole is an initial/critical step of ciliogenesis, but the mechanisms are unclear. Here, we demonstrate that myosin-Va mediates the transportation of preciliary vesicles to the mother centriole and reveal the underlying mechanism. We also show that the myosin-Va-mediated transportation of preciliary vesicles is the earliest event that defines the onset of ciliogenesis...
January 15, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29311657/author-correction-tbc1d23-is-a-bridging-factor-for-endosomal-vesicle-capture-by-golgins-at-the-trans-golgi
#5
John J H Shin, Alison K Gillingham, Farida Begum, Jessica Chadwick, Sean Munro
In the version of Supplementary Table 1 originally published with this Article, in the sheet relating to Fig. 3c, all values in the 'golgin-97-mito' column were 1.3 times larger than the actual values, which was due to author error when generating the Supplementary Table. These errors did not affect the graph in Fig. 3c, which was plotted with the correct values. Supplementary Table 1 has now been replaced so that it contains the correct values.
January 8, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29311656/defining-murine-organogenesis-at-single-cell-resolution-reveals-a-role-for-the-leukotriene-pathway-in-regulating-blood-progenitor-formation
#6
Ximena Ibarra-Soria, Wajid Jawaid, Blanca Pijuan-Sala, Vasileios Ladopoulos, Antonio Scialdone, David J Jörg, Richard C V Tyser, Fernando J Calero-Nieto, Carla Mulas, Jennifer Nichols, Ludovic Vallier, Shankar Srinivas, Benjamin D Simons, Berthold Göttgens, John C Marioni
During gastrulation, cell types from all three germ layers are specified and the basic body plan is established 1 . However, molecular analysis of this key developmental stage has been hampered by limited cell numbers and a paucity of markers. Single-cell RNA sequencing circumvents these problems, but has so far been limited to specific organ systems 2 . Here, we report single-cell transcriptomic characterization of >20,000 cells immediately following gastrulation at E8.25 of mouse development. We identify 20 major cell types, which frequently contain substructure, including three distinct signatures in early foregut cells...
January 8, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29255172/mechanical-cues-control-mutant-p53-stability-through-a-mevalonate-rhoa-axis
#7
Eleonora Ingallina, Giovanni Sorrentino, Rebecca Bertolio, Kamil Lisek, Alessandro Zannini, Luca Azzolin, Luisa Ulloa Severino, Denis Scaini, Miguel Mano, Fiamma Mantovani, Antonio Rosato, Silvio Bicciato, Stefano Piccolo, Giannino Del Sal
Tumour-associated p53 missense mutants act as driver oncogenes affecting cancer progression, metastatic potential and drug resistance (gain-of-function) 1 . Mutant p53 protein stabilization is a prerequisite for gain-of-function manifestation; however, it does not represent an intrinsic property of p53 mutants, but rather requires secondary events 2 . Moreover, mutant p53 protein levels are often heterogeneous even within the same tumour, raising questions on the mechanisms that control local mutant p53 accumulation in some tumour cells but not in their neighbours 2,3 ...
December 18, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29230017/systematic-analysis-of-ribophagy-in-human-cells-reveals-bystander-flux-during-selective-autophagy
#8
Heeseon An, J Wade Harper
Ribosomes are abundant cellular machines 1,2 that are regulated by assembly, supernumerary subunit turnover and nascent chain quality control mechanisms 1-5 . Moreover, nitrogen starvation in yeast has been reported to promote selective ribosome delivery to the vacuole in an autophagy conjugation system dependent manner, a process called 'ribophagy' 6,7 . However, whether ribophagy in mammals is selective or regulated is unclear. Using Ribo-Keima flux reporters, we find that starvation or mTOR inhibition promotes VPS34-dependent ribophagic flux, which, unlike yeast, is largely independent of ATG8 conjugation and occurs concomitantly with other cytosolic protein autophagic flux reporters 8,9 ...
December 11, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29230015/a-perk-mir-211-axis-suppresses-circadian-regulators-and-protein-synthesis-to-promote-cancer-cell-survival
#9
Yiwen Bu, Akihiro Yoshida, Nilesh Chitnis, Brian J Altman, Feven Tameire, Amanda Oran, Victoria Gennaro, Kent E Armeson, Steven B McMahon, Gerald B Wertheim, Chi V Dang, Davide Ruggero, Constantinos Koumenis, Serge Y Fuchs, J Alan Diehl
The unfolded protein response (UPR) is a stress-activated signalling pathway that regulates cell proliferation, metabolism and survival. The circadian clock coordinates metabolism and signal transduction with light/dark cycles. We explore how UPR signalling interfaces with the circadian clock. UPR activation induces a 10 h phase shift in circadian oscillations through induction of miR-211, a PERK-inducible microRNA that transiently suppresses both Bmal1 and Clock, core circadian regulators. Molecular investigation reveals that miR-211 directly regulates Bmal1 and Clock via distinct mechanisms...
December 11, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29203884/a-homeostatic-apical-microtubule-network-shortens-cells-for-epithelial-folding-via-a-basal-polarity-shift
#10
Michiko Takeda, Mustafa M Sami, Yu-Chiun Wang
Epithelial folding is typically driven by localized actomyosin contractility. However, it remains unclear how epithelia deform when myosin levels are low and uniform. In the Drosophila gastrula, dorsal fold formation occurs despite a lack of localized myosin changes, while the fold-initiating cells reduce cell height following basal shifts of polarity via an unknown mechanism. We show that cell shortening depends on an apical microtubule network organized by the CAMSAP protein Patronin. Prior to gastrulation, microtubule forces generated by the minus-end motor dynein scaffold the apical cell cortex into a dome-like shape, while the severing enzyme Katanin facilitates network remodelling to ensure tissue-wide cell size homeostasis...
December 4, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29131140/a-transient-pool-of-nuclear-f-actin-at-mitotic-exit-controls-chromatin-organization
#11
Christian Baarlink, Matthias Plessner, Alice Sherrard, Kohtaro Morita, Shinji Misu, David Virant, Eva-Maria Kleinschnitz, Robert Harniman, Dominic Alibhai, Stefan Baumeister, Kei Miyamoto, Ulrike Endesfelder, Abderrahmane Kaidi, Robert Grosse
Re-establishment of nuclear structure and chromatin organization after cell division is integral for genome regulation or development and is frequently altered during cancer progression. The mechanisms underlying chromatin expansion in daughter cells remain largely unclear. Here, we describe the transient formation of nuclear actin filaments (F-actin) during mitotic exit. These nuclear F-actin structures assemble in daughter cell nuclei and undergo dynamic reorganization to promote nuclear protrusions and volume expansion throughout early G1 of the cell cycle...
November 13, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29084199/class-iii-phosphatidylinositol-3-oh-kinase-controls-epithelial-integrity-through-endosomal-lkb1-regulation
#12
Fergal O'Farrell, Viola Hélène Lobert, Marte Sneeggen, Ashish Jain, Nadja Sandra Katheder, Eva Maria Wenzel, Sebastian Wolfgang Schultz, Kia Wee Tan, Andreas Brech, Harald Stenmark, Tor Erik Rusten
The molecular mechanisms underlying the interdependence between intracellular trafficking and epithelial cell polarity are poorly understood. Here we show that inactivation of class III phosphatidylinositol-3-OH kinase (CIII-PI3K), which produces phosphatidylinositol-3-phosphate (PtdIns3P) on endosomes, disrupts epithelial organization. This is caused by dysregulation of endosomally localized Liver Kinase B1 (LKB1, also known as STK11), which shows delocalized and increased activity accompanied by dysplasia-like growth and invasive behaviour of cells provoked by JNK pathway activation...
October 30, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29084198/distinct-kinetics-of-serine-and-threonine-dephosphorylation-are-essential-for-mitosis
#13
Jamin B Hein, Emil P T Hertz, Dimitriya H Garvanska, Thomas Kruse, Jakob Nilsson
Protein phosphatase 2A (PP2A) in complex with B55 regulatory subunits reverses cyclin-dependent kinase 1 (Cdk1) phosphorylations at mitotic exit. Interestingly, threonine and serine residues phosphorylated by Cdk1 display distinct phosphorylation dynamics, but the biological significance remains unexplored. Here we demonstrate that the phosphothreonine preference of PP2A-B55 provides an essential regulatory element of mitotic exit. To allow rapid activation of the anaphase-promoting complex/cyclosome (APC/C) co-activator Cdc20, inhibitory phosphorylation sites are conserved as threonines while serine substitutions delay dephosphorylation and Cdc20 activation...
October 30, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29269951/mechanoreciprocity-in-cell-migration
#14
REVIEW
Sjoerd van Helvert, Cornelis Storm, Peter Friedl
Cell migration is an adaptive process that depends on and responds to physical and molecular triggers. Moving cells sense and respond to tissue mechanics and induce transient or permanent tissue modifications, including extracellular matrix stiffening, compression and deformation, protein unfolding, proteolytic remodelling and jamming transitions. Here we discuss how the bi-directional relationship of cell-tissue interactions (mechanoreciprocity) allows cells to change position and contributes to single-cell and collective movement, structural and molecular tissue organization, and cell fate decisions...
January 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29269950/sugar-fuels-t-cell-memory
#15
Joanna Olivas, Tiffany Horng
No abstract text is available yet for this article.
January 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29269949/perk-links-the-clock-and-protein-stress-in-cancer
#16
Miguel Sanchez-Alvarez, Chris Bakal
No abstract text is available yet for this article.
January 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29269948/muscling-toward-therapy-with-erbb3-and-ngfr
#17
Andrew T V Ho, Helen M Blau
No abstract text is available yet for this article.
January 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29269947/supporting-the-sharing-of-research
#18
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
January 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29255173/the-autophagy-receptor-allo-1-and-the-ikke-1-kinase-control-clearance-of-paternal-mitochondria-in-caenorhabditis-elegans
#19
Miyuki Sato, Katsuya Sato, Kotone Tomura, Hidetaka Kosako, Ken Sato
In Caenorhabditis elegans embryos, paternally provided organelles, including mitochondria, are eliminated by a process of selective autophagy called allophagy, the mechanism by which mitochondrial DNA is inherited maternally. However, it remains unclear how paternal organelles are recognized and targeted for autophagy. Here, we identified an autophagy receptor for allophagy, ALLO-1. ALLO-1 is essential for autophagosome formation around paternal organelles and directly binds to the worm LC3 homologue LGG-1 through its LC3-interacting region (LIR) motif...
January 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29255171/erbb3-and-ngfr-mark-a-distinct-skeletal-muscle-progenitor-cell-in-human-development-and-hpscs
#20
Michael R Hicks, Julia Hiserodt, Katrina Paras, Wakana Fujiwara, Ascia Eskin, Majib Jan, Haibin Xi, Courtney S Young, Denis Evseenko, Stanley F Nelson, Melissa J Spencer, Ben Van Handel, April D Pyle
Human pluripotent stem cells (hPSCs) can be directed to differentiate into skeletal muscle progenitor cells (SMPCs). However, the myogenicity of hPSC-SMPCs relative to human fetal or adult satellite cells remains unclear. We observed that hPSC-SMPCs derived by directed differentiation are less functional in vitro and in vivo compared to human satellite cells. Using RNA sequencing, we found that the cell surface receptors ERBB3 and NGFR demarcate myogenic populations, including PAX7 progenitors in human fetal development and hPSC-SMPCs...
January 2018: Nature Cell Biology
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