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Y-Q Li, Zw-C Cheng, Sk-W Liu, I Aubert, C S Wong
Inhibition of hippocampal neurogenesis is implicated in neurocognitive dysfunction after cranial irradiation for brain tumors. How irradiation results in impaired neuronal development remains poorly understood. The Trp53 (p53) gene is known to regulate cellular DNA damage response after irradiation. Whether it has a role in disruption of late neuronal development remains unknown. Here we characterized the effects of p53 on neuronal development in adult mouse hippocampus after irradiation. Different bromodeoxyuridine incorporation paradigms and a transplantation study were used for cell fate mapping...
2016: Cell Death Discovery
Agata Stryjewska, Ruben Dries, Tim Pieters, Griet Verstappen, Andrea Conidi, Kathleen Coddens, Annick Francis, Lieve Umans, Wilfred F J van IJcken, Geert Berx, Leo A van Grunsven, Frank Grosveld, Steven Goossens, Jody J Haigh, Danny Huylebroeck
In human ESCs the transcription factor Zeb2 regulates neuroectoderm versus mesendoderm formation, but it is unclear how Zeb2 affects the global transcriptional regulatory network in these cell-fate decisions. We generated Zeb2 knockout (KO) mouse ESCs, subjected them as embryoid bodies (EBs) to neural and general differentiation and carried out temporal RNA-sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS) analysis in neural differentiation. This shows that Zeb2 acts preferentially as a transcriptional repressor associated with developmental progression and that Zeb2 KO ESCs can exit from their naïve state...
October 14, 2016: Stem Cells
Pia Rantakari, Norma Jäppinen, Emmi Lokka, Elias Mokkala, Heidi Gerke, Emilia Peuhu, Johanna Ivaska, Kati Elima, Kaisa Auvinen, Marko Salmi
Macrophages are required for normal embryogenesis, tissue homeostasis and immunity against microorganisms and tumours. Adult tissue-resident macrophages largely originate from long-lived, self-renewing embryonic precursors and not from haematopoietic stem-cell activity in the bone marrow. Although fate-mapping studies have uncovered a great amount of detail on the origin and kinetics of fetal macrophage development in the yolk sac and liver, the molecules that govern the tissue-specific migration of these cells remain completely unknown...
October 12, 2016: Nature
Shanni N Silberberg, Leila Taher, Susan Lindtner, Magnus Sandberg, Alex S Nord, Daniel Vogt, Gabriel L Mckinsey, Renee Hoch, Kartik Pattabiraman, Dongji Zhang, Jose L Ferran, Aleksandar Rajkovic, Olga Golonzhka, Carol Kim, Hongkui Zeng, Luis Puelles, Axel Visel, John L R Rubenstein
Elucidating the transcriptional circuitry controlling forebrain development requires an understanding of enhancer activity and regulation. We generated stable transgenic mouse lines that express CreER(T2) and GFP from ten different enhancer elements with activity in distinct domains within the embryonic basal ganglia. We used these unique tools to generate a comprehensive regional fate map of the mouse subpallium, including sources for specific subtypes of amygdala neurons. We then focused on deciphering transcriptional mechanisms that control enhancer activity...
October 5, 2016: Neuron
Mubing Duan, Margaret L Hibbs, Weisan Chen
The lung myeloid cell microenvironment comprises airway, alveolar and interstitial macrophages, peripheral blood recruited lung monocytes as well as residential and migratory dendritic cell subsets. Findings from fate mapping, parabiosis, transcriptome and epigenome profiling studies now indicate that tissue macrophage and monocyte subsets possess specialized functions which differentially impact homoeostatic tolerance, pathogen detection and pathogen killing. In the lungs, residential alveolar macrophages are catabolic and immunosuppressive in contrast to the classically pro-inflammatory repertoire of lung monocytes and monocyte-derived dendritic cells recruited during acute inflammation...
October 18, 2016: Immunology and Cell Biology
Manreet Padwal, Peter J Margetts
Peritoneal fibrosis is one of the major complications occurring in long-term peritoneal dialysis patients as a result of injury. Peritoneal fibrosis is characterized by submesothelial thickening and fibrosis which is associated with a decline in peritoneal membrane function. The myofibroblast has been identified as the key player involved in the development and progression of peritoneal fibrosis. Activation of the myofibroblast is correlated with expansion of the extracellular matrix and changes in peritoneal membrane integrity...
September 2016: Kidney Research and Clinical Practice
Joanna Burger, Michael Gochfeld
BACKGROUND: At most contaminated sites the risk to workers focuses on those 'hazardous waste workers' directly exposed to chemicals or radionuclides, and to the elaborate approaches implemented to protecting their health and safety. Ecological workers generally are not considered. OBJECTIVES: To explore the risks to the health and safety of ecological workers on sites with potential chemical and radiological exposures before, during or after remediation of contamination...
2016: Journal of Community Medicine & Health Education
Marco-Antonio Mendoza-Parra, Valeriya Malysheva, Mohamed Ashick Mohamed Saleem, Michele Lieb, Aurelie Godel, Hinrich Gronemeyer
Cell lineages, which shape the body architecture and specify cell functions, derive from the integration of a plethora of cell intrinsic and extrinsic signals. These signals trigger a multiplicity of decisions at several levels to modulate the activity of dynamic gene regulatory networks (GRNs), which ensure both general and cell-specific functions within a given lineage, thereby establishing cell fates. Significant knowledge about these events and the involved key drivers comes from homogeneous cell differentiation models...
September 20, 2016: Genome Research
João Francisco Botelho, Daniel Smith-Paredes, Sergio Soto-Acuña, Daniel Núñez-León, Verónica Palma, Alexander O Vargas
In early theropod dinosaurs-the ancestors of birds-the hallux (digit 1) had an elevated position within the foot and had lost the proximal portion of its metatarsal. It no longer articulated with the ankle, but was attached at about mid-length of metatarsal 2 (mt2). In adult birds, the hallux is articulated closer to the distal end of mt2 at ground level with the other digits. However, on chick embryonic day 7, its position is as in early theropods at half-length of mt2. The adult distal location is acquired during embryonic days 8-10...
September 21, 2016: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
Yvonne Neumann, Svenja A Bruns, Manfred Rohde, Tomasz K Prajsnar, Simon J Foster, Ingo Schmitz
Autophagy, a catabolic pathway of lysosomal degradation, acts not only as an efficient recycle and survival mechanism during cellular stress, but also as an anti-infective machinery. The human pathogen Staphylococcus aureus (S. aureus) was originally considered solely as an extracellular bacterium, but is now recognized additionally to invade host cells, which might be crucial for persistence. However, the intracellular fate of S. aureus is incompletely understood. Here, we show for the first time induction of selective autophagy by S...
September 14, 2016: Autophagy
Julien Guy, Alexandra Sachkova, Martin Möck, Mirko Witte, Robin J Wagener, Jochen F Staiger
Layer IV (LIV) of the rodent somatosensory cortex contains the somatotopic barrel field. Barrels receive much of the sensory input to the cortex through innervation by thalamocortical axons from the ventral posteromedial nucleus. In the reeler mouse, the absence of cortical layers results in the formation of mispositioned barrel-equivalent clusters of LIV fated neurons. Although functional imaging suggests that sensory input activates the cortex, little is known about the cellular and synaptic properties of identified excitatory neurons of the reeler cortex...
September 12, 2016: Cerebral Cortex
Thomas Höfer, Hans-Reimer Rodewald
The hematopoietic stem cell (HSC) compartment must be maintained life-long, while being replenishable only from within. HSC proliferation can compensate for cell loss by differentiation, by cell death, or by mobilization from the bone marrow niches, but the relative use of proliferation to compensate for these distinct depletion sources is unclear. Classifications of HSC states (e.g., as active, dormant, quiescent or parsimonious) have mostly been based on HSC proliferation rather than on actual differentiation arising from HSC...
September 10, 2016: Current Opinion in Cell Biology
Miao He, Jason Tucciarone, SooHyun Lee, Maximiliano José Nigro, Yongsoo Kim, Jesse Maurica Levine, Sean Michael Kelly, Illya Krugikov, Priscilla Wu, Yang Chen, Lin Gong, Yongjie Hou, Pavel Osten, Bernardo Rudy, Z Josh Huang
Systematic genetic access to GABAergic cell types will facilitate studying the function and development of inhibitory circuitry. However, single gene-driven recombinase lines mark relatively broad and heterogeneous cell populations. Although intersectional approaches improve precision, it remains unclear whether they can capture cell types defined by multiple features. Here we demonstrate that combinatorial genetic and viral approaches target restricted GABAergic subpopulations and cell types characterized by distinct laminar location, morphology, axonal projection, and electrophysiological properties...
September 21, 2016: Neuron
Qingzhong Ren, Takeshi Awasaki, Yu-Fen Huang, Zhiyong Liu, Tzumin Lee
The morphology and physiology of neurons are directed by developmental decisions made within their lines of descent from single stem cells. Distinct stem cells may produce neurons having shared properties that define their cell class, such as the type of secreted neurotransmitter. The relationship between cell class and lineage is complex. Here we developed the transgenic cell class-lineage intersection (CLIn) system to assign cells of a particular class to specific lineages within the Drosophila brain. CLIn also enables birth-order analysis and genetic manipulation of particular cell classes arising from particular lineages...
October 10, 2016: Current Biology: CB
Emilie Legué, Jackie L Gottshall, Edouard Jaumouillé, Alberto Roselló-Díez, Wei Shi, Luis Humberto Barraza, Senna Washington, Rachel L Grant, Alexandra L Joyner
BACKGROUND: The mouse cerebellum (Cb) has a remarkably complex foliated three-dimensional (3D) structure, but a stereotypical cytoarchitecture and local circuitry. Little is known of the cellular behaviors and genes that function during development to determine the foliation pattern. In the anteroposterior axis the mammalian cerebellum is divided by lobules with distinct sizes, and the foliation pattern differs along the mediolateral axis defining a medial vermis and two lateral hemispheres...
2016: Neural Development
Susanne Kleiderman, Simon Gutbier, Kemal Ugur Tufekci, Felipe Ortega, João V Sá, Ana P Teixeira, Catarina Brito, Enrico Glaab, Benedikt Berninger, Paula M Alves, Marcel Leist
Conversion of astrocytes to neurons, via de-differentiation to neural stem cells (NSC), may be a new approach to treat neurodegenerative diseases and brain injuries. The signaling factors affecting such a cell conversion are poorly understood, and they are hard to identify in complex disease models or conventional cell cultures. To address this question, we developed a serum-free, strictly controlled culture system of pure and homogeneous 'astrocytes generated form murine embryonic stem cells (ESC)'. These stem cell derived astrocytes (mAGES), as well as standard primary astrocytes resumed proliferation upon addition of FGF...
September 7, 2016: Stem Cells
Kiran Kumar Bokara, Jae Hwan Kim, Jae Young Kim, Jong Eun Lee
Growing evidence suggests that the clinical use of neural progenitor cells (NPCs) is hampered by heterogeneity, poor neuronal yield and low survival rate. Recently, we reported that retrovirus-delivered human arginine decarboxylase (hADC) genes improve cell survival against oxidative insult in murine NPCs in vitro. This study investigates whether the induced expression of hADC gene in mNPCs induces any significant change in the cell fate commitment. The evaluation of induced hADC gene function was assessed by knockdown of hADC gene using specific siRNA...
August 17, 2016: Stem Cell Research
Francesco Trepiccione, Christelle Soukaseum, Anna Iervolino, Federica Petrillo, Miriam Zacchia, Gunther Schütz, Dominique Eladari, Giovambattista Capasso, Juliette Hadchouel
The distal nephron is a heterogeneous part of the nephron composed by six different cell types forming the epithelium of the distal convolute (DCT), connecting (CNT) and collecting duct (CD). To dissect the function of these cells, knock out models specific for their unique cell marker have been created. However, since this part of the nephron develops at the border between the ureteric bud and the metanephric mesenchyme, the specificity of the single cell-markers has been recently questioned. Here, by mapping the fate of the AQP2, NCC-positive cells using transgenic mouse lines expressing the YFP fluorescent marker, we showed that the origin of the distal nephron is extremely composite...
August 31, 2016: American Journal of Physiology. Renal Physiology
Héctor Cervera, Jasna Lalić, Santiago F Elena
: Adaptive fitness landscapes are a fundamental concept in evolutionary biology that relate the genotype of individuals with their fitness. At the end, the evolutionary fate of evolving populations depends on the topography of the landscape, that is, the number of accessible mutational pathways and of possible fitness peaks (i.e, adaptive solutions). For long time, fitness landscapes were only theoretical constructions due to a lack of precise information on the mapping between genotypes and phenotypes...
August 31, 2016: Journal of Virology
Jasper J Koning, Tanja Konijn, Kim A Lakeman, Tom O'Toole, Keane J G Kenswil, Marc H G P Raaijmakers, Tatyana V Michurina, Grigori Enikolopov, Reina E Mebius
During embryogenesis, lymph nodes form through intimate interaction between lymphoid tissue inducer and lymphoid tissue organizer (LTo) cells. Shortly after birth in mice, specialized stromal cell subsets arise that organize microenvironments within the lymph nodes; however, their direct precursors have not yet been identified. In the bone marrow, mesenchymal stem cells are labeled with GFP in nestin-GFP mice, and we show that during all stages of development, nestin(+) cells are present within lymph nodes of these mice...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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