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https://www.readbyqxmd.com/read/29142505/targeting-deubiquitinating-enzymes-in-cancer-stem-cells
#1
REVIEW
Hu Lei, Huizhuang Shan, Yingli Wu
Cancer stem cells (CSCs) are rare but accounted for tumor initiation, progression, metastasis, relapse and therapeutic resistance. Ubiquitination and deubiquitination of stemness-related proteins are essential for CSC maintenance and differentiation, even leading to execute various stem cell fate choices. Deubiquitinating enzymes (DUBs), specifically disassembling ubiquitin chains, are important to maintain the balance between ubiquitination and deubiquitination. In this review, we have focused on the DUBs regulation of stem cell fate determination...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29141582/a-novel-interaction-between-kinase-activities-in-regulation-of-cilia-formation
#2
Nicole DeVaul, Katerina Koloustroubis, Rong Wang, Ann O Sperry
BACKGROUND: The primary cilium is an extension of the cell membrane that encloses a microtubule-based axoneme. Primary cilia are essential for transmission of environmental cues that determine cell fate. Disruption of primary cilia function is the molecular basis of numerous developmental disorders. Despite their biological importance, the mechanisms governing their assembly and disassembly are just beginning to be understood. Cilia growth and disassembly are essential events when cells exit and reenter into the cell cycle...
November 15, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/29137121/human-mesenchymal-stem-cells-growth-and-osteogenic-differentiation-on-piezoelectric-poly-vinylidene-fluoride-microsphere-substrates
#3
R Sobreiro-Almeida, M N Tamaño-Machiavello, E O Carvalho, L Cordón, S Doria, L Senent, D M Correia, C Ribeiro, S Lanceros-Méndez, R Sabater I Serra, J L Gomez Ribelles, A Sempere
The aim of this work was to determine the influence of the biomaterial environment on human mesenchymal stem cell (hMSC) fate when cultured in supports with varying topography. Poly(vinylidene fluoride) (PVDF) culture supports were prepared with structures ranging between 2D and 3D, based on PVDF films on which PVDF microspheres were deposited with varying surface density. Maintenance of multipotentiality when cultured in expansion medium was studied by flow cytometry monitoring the expression of characteristic hMSCs markers, and revealed that cells were losing their characteristic surface markers on these supports...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29136113/the-laminar-organization-of-piriform-cortex-follows-a-selective-developmental-and-migratory-program-established-by-cell-lineage
#4
Eduardo Martin-Lopez, Kimiko Ishiguro, Charles A Greer
Piriform cortex (PC) is a 3-layer paleocortex receiving primary afferent input from the olfactory bulb. The past decade has seen significant progress in understanding the synaptic, cellular and functional organization of PC, but PC embryogenesis continues to be enigmatic. Here, using birthdating strategies and clonal analyses, we probed the early development and laminar specificity of neurogenesis/gliogenesis as it relates to the organization of the PC. Our data demonstrate a temporal sequence of laminar-specific neurogenesis following the canonical "inside-out" pattern, with the notable exception of PC Layer II which exhibited an inverse "outside-in" temporal neurogenic pattern...
November 9, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29135921/nox-reactive-oxygen-species-and-regulation-of-vascular-cell-fate
#5
REVIEW
Denise Burtenshaw, Roya Hakimjavadi, Eileen M Redmond, Paul A Cahill
The generation of reactive oxygen species (ROS) and an imbalance of antioxidant defence mechanisms can result in oxidative stress. Several pro-atherogenic stimuli that promote intimal-medial thickening (IMT) and early arteriosclerotic disease progression share oxidative stress as a common regulatory pathway dictating vascular cell fate. The major source of ROS generated within the vascular system is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (Nox), of which seven members have been characterized...
November 14, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29131550/innate-and-acquired-immune-surveillance-in-the-post-dissemination-phase-of-metastasis
#6
REVIEW
Hugo Gonzalez, Isabella Robles, Zena Werb
Metastasis is responsible for the majority of death in cancer patients. Of the different steps in the metastasis cascade, the post-dissemination phase is perhaps one of the least understood. Many factors, both from the disseminated tumor cells (DTCs) and the microenvironment, impact the success of the metastatic outgrowth. In this article, we discuss the interactions between colonizing cancer cells and immune cells in the period between vascular arrest in a secondary organ and metastatic outgrowth. We address the ambiguity in the findings of current research regarding the role of immune cells in regulating the metastatic microenvironment, and their hand in determining cancer cell fate...
November 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29129916/a-post-transcriptional-program-coordinated-by-csde1-prevents-intrinsic-neural-differentiation-of-human-embryonic-stem-cells
#7
Hyun Ju Lee, Deniz Bartsch, Cally Xiao, Santiago Guerrero, Gaurav Ahuja, Christina Schindler, James J Moresco, John R Yates, Fátima Gebauer, Hisham Bazzi, Christoph Dieterich, Leo Kurian, David Vilchez
While the transcriptional network of human embryonic stem cells (hESCs) has been extensively studied, relatively little is known about how post-transcriptional modulations determine hESC function. RNA-binding proteins play central roles in RNA regulation, including translation and turnover. Here we show that the RNA-binding protein CSDE1 (cold shock domain containing E1) is highly expressed in hESCs to maintain their undifferentiated state and prevent default neural fate. Notably, loss of CSDE1 accelerates neural differentiation and potentiates neurogenesis...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29128333/nf-%C3%AE%C2%BAb-dynamics-discriminate-between-tnf-doses-in-single-cells
#8
Qiuhong Zhang, Sanjana Gupta, David L Schipper, Gabriel J Kowalczyk, Allison E Mancini, James R Faeder, Robin E C Lee
Although cytokine-dependent dynamics of nuclear factor κB (NF-κB) are known to encode information that regulates cell fate decisions, it is unclear whether single-cell responses are switch-like or encode more information about cytokine dose. Here, we measure the dynamic subcellular localization of NF-κB in response to a range of tumor necrosis factor (TNF) stimulation conditions to determine the prevailing mechanism of single-cell dose discrimination. Using an information theory formalism that accounts for signaling dynamics and non-responsive cell subpopulations, we find that the information transmission capacity of single cells exceeds that predicted from a switch-like response...
November 7, 2017: Cell Systems
https://www.readbyqxmd.com/read/29123025/mitogen-activated-protein-kinase-mapk-dynamics-determine-cell-fate-in-the-yeast-mating-response
#9
Yang Li, Julie Roberts, Zohreh AkhavanAghdam, Nan Hao
In the yeast Saccharomyces cerevisiae, the exposure to mating pheromone activates a prototypic mitogen-activated protein kinase (MAPK) cascade and triggers a dose-dependent differentiation response. Whereas a high pheromone dose induces growth arrest and formation of a shmoo-like morphology in yeast cells, lower pheromone doses elicit elongated cell growth. Previous population-level analysis has revealed that the MAPK Fus3 plays an important role in mediating this differentiation switch. To further investigate how Fus3 controls the fate decision process at the single-cell level, we developed a specific translocation-based reporter for monitoring Fus3 activity in individual live cells...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29120519/palovarotene-inhibits-osteochondroma-formation-in-a-mouse-model-of-multiple-hereditary-exostoses
#10
Toshihiro Inubushi, Isabelle Lemire, Fumitoshi Irie, Yu Yamaguchi
Multiple hereditary exostoses (MHE), also known as multiple osteochondromas (MO), is an autosomal dominant disorder characterized by the development of multiple cartilage-capped bone tumors (osteochondromas). The large majority of patients with MHE carry loss-of-function mutations in the EXT1 or EXT2 gene, which encodes a glycosyltransferase essential for heparan sulfate (HS) biosynthesis. Increasing evidence suggests that enhanced BMP signaling resulting from loss of HS expression plays a role in osteochondroma formation in MHE...
November 9, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29119536/turning-death-to-growth-hematopoietic-growth-factors-promote-neurite-outgrowth-through-mek-erk-p53-pathway
#11
Mei Gao, Li-Ru Zhao
Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are the essential hematopoietic growth factors to control hematopoiesis. However, the role of SCF and G-CSF in the central nervous system remains poorly understood. Here, we have demonstrated the involvement of MEK/ERK/p53 signaling in SCF + G-CSF-enhanced neurite extension. Cortical neurons dissected from embryonic rat brains were seeded onto the membranes of transwell inserts, and neurite outgrowth was determined by using both the neurite outgrowth quantification assay kit and immunostaining of β III tubulin...
November 8, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29118092/structure-based-discovery-of-cyclin-dependent-protein-kinase-inhibitors
#12
REVIEW
Mathew P Martin, Jane A Endicott, Martin E M Noble
The cell fate-determining roles played by members of the cyclin-dependent protein kinase (CDK) family explain why their dysregulation can promote proliferative diseases, and identify them as potential targets for drug discovery in oncology and beyond. After many years of research, the first efficacious CDK inhibitors have now been registered for clinical use in a defined segment of breast cancer. Research is underway to identify inhibitors with appropriate CDK-inhibitory profiles to recapitulate this success in other disease settings...
November 8, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/29118075/translational-control-of-a-human-cdkn1a-mrna-splice-variant-regulates-the-fate-of-uvb-irradiated-human-keratinocytes
#13
Ann E Collier, Dan F Spandau, Ronald C Wek
In response to sublethal UVB irradiation, human keratinocytes transiently block progression of the cell cycle to allow ample time for DNA repair and cell fate determination. These cellular activities are important for evading the initiation of carcinogenesis in skin. Central to these processes is the repression of initiation of mRNA translation through GCN2 phosphorylation of eIF2α (eIF2α-P). Concurrent with reduced global protein synthesis, eIF2α-P and the accompanying Integrated stress response (ISR) selectively enhance translation of mRNAs involved in stress adaptation...
November 8, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29114030/near-cognate-codons-contribute-complexity-to-translation-regulation
#14
N Louise Glass
The interplay between translation initiation, modification of translation initiation factors, and selection of start sites on mRNA for protein synthesis can play a regulatory role in the cellular response to stress, development, and cell fate in eukaryotic species by shaping the proteome. As shown by Ivanov et al. (mBio 8:e00844-17, 2017, https://doi.org/10.1128/mBio.00844-17), in the filamentous fungus Neurospora crassa, both upstream open reading frames (uORFs) and near-cognate start codons negatively or positively regulate the translation of the transcription factor CPC1 and production of CPC1 isoforms, which mediate the cellular response to amino acid starvation...
November 7, 2017: MBio
https://www.readbyqxmd.com/read/29113750/epigenetic-regulation-of-astrocyte-function-in-neuroinflammation-and-neurodegeneration
#15
REVIEW
Matthew Neal, Jason R Richardson
Epigenetic mechanisms control various functions throughout the body, from cell fate determination in development to immune responses and inflammation. Neuroinflammation is one of the prime contributors to the initiation and progression of neurodegeneration in a variety of diseases, including Alzheimer's and Parkinson's diseases. Because astrocytes are the largest population of glial cells, they represent an important regulator of CNS function, both in health and disease. Only recently have studies begun to identify the epigenetic mechanisms regulating astrocyte responses in neurodegenerative diseases...
November 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29110606/the-fate-of-in-situ-lens-regeneration-is-determined-by-capsulorhexis-size
#16
X Tan, Z Liu, Y Zhu, C Chen, S Huang, B Chen, Z Lin, J Chen, X Tang, B Qu, X Liu, L Luo, J Deng, F Shang, M Wu, W Chen, H Lin, Y Liu
BACKGROUND AND OBJECTIVE: Lens regeneration is an optimal strategy for cataract patients to regain visual acuity with accommodation. We recently designed a novel, minimally invasive capsulorhexis surgical method for cataract removal that achieved functional lens regeneration in human infants. However, small anterior capsulorhexis requires advanced surgical expertise. To know whether the quality of the regenerated lens can be maintained with enlarged anterior capsulorhexis, we investigated the shape and transparency of the regenerated lenses with different anterior capsulorhexis diameters (ACDs)...
November 5, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/29110400/spaghetti-a-homolog-of-human-rpap3-rna-polymerase-ii-associated-protein-3-determines-the-fate-of-germline-stem-cells-in-drosophila-ovary
#17
Dongsheng Chen, Xiaoqian Tao, Lijuan Zhou, Fuling Sun, Mingzhong Sun, Xin Fang
The Drosophila ovary provides an attractive model for studying the extrinsic or intrinsic factors that regulate the fate of germline stem cells (GSCs). Using this model, we identified a new role for Drosophila spaghetti (spag), encoding a homolog of human RNA polymerase II-associated protein 3 (RPAP3), in regulating the fate of ovarian GSCs. Results from spag knockdown and genetic mosaic studies suggest that spag functions as an intrinsic factor for GSCs maintenance. Loss of Spag by, either spag RNAi or null mutation failed to trigger apoptosis in ovarian GSCs...
November 7, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29107558/esrp1-mutations-cause-hearing-loss-due-to-defects-in-alternative-splicing-that-disrupt-cochlear-development
#18
Alex M Rohacek, Thomas W Bebee, Richard K Tilton, Caleb M Radens, Chris McDermott-Roe, Natoya Peart, Maninder Kaur, Michael Zaykaner, Benjamin Cieply, Kiran Musunuru, Yoseph Barash, John A Germiller, Ian D Krantz, Russ P Carstens, Douglas J Epstein
Alternative splicing contributes to gene expression dynamics in many tissues, yet its role in auditory development remains unclear. We performed whole-exome sequencing in individuals with sensorineural hearing loss (SNHL) and identified pathogenic mutations in Epithelial Splicing-Regulatory Protein 1 (ESRP1). Patient-derived induced pluripotent stem cells showed alternative splicing defects that were restored upon repair of an ESRP1 mutant allele. To determine how ESRP1 mutations cause hearing loss, we evaluated Esrp1(-/-) mouse embryos and uncovered alterations in cochlear morphogenesis, auditory hair cell differentiation, and cell fate specification...
November 6, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29107380/the-fate-of-multilamellar-bodies-produced-and-secreted-by-dictyostelium-discoideum-amoebae
#19
Alix M Denoncourt, Alicia F Durocher, Valérie E Paquet, Steve J Charette
The amoeba Dictyostelium discoideum produces and secretes multilamellar bodies (MLBs) mainly composed of amoebal membranes upon digestion of bacteria. After their secretion, the fate of these MLBs remains unknown. The aim of this study was to determine if protozoa can internalize and digest secreted D. discoideum MLBs. Our results showed that MLBs were ingested by naive axenic D. discoideum cells (i. e. cells not exposed to bacteria and consequently not producing MLBs). Only a small fraction of the ingested MLBs were found in cells' post-lysosomes compared to undigestible beads suggesting that naive amoebae digest them...
October 14, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29107300/adult-neural-stem-cell-fate-is-determined-by-thyroid-hormone-activation-of-mitochondrial-metabolism
#20
J D Gothié, A Sébillot, C Luongo, M Legendre, C Nguyen Van, K Le Blay, M Perret-Jeanneret, S Remaud, B A Demeneix
OBJECTIVE: In the adult brain, neural stem cells (NSCs) located in the subventricular zone (SVZ) produce both neuronal and glial cells. Thyroid hormones (THs) regulate adult NSC differentiation towards a neuronal phenotype, but also have major roles in mitochondrial metabolism. As NSC metabolism relies mainly on glycolysis, whereas mature cells preferentially use oxidative phosphorylation, we studied how THs and mitochondrial metabolism interact on NSC fate determination. METHODS: We used a mitochondrial membrane potential marker in vivo to analyze mitochondrial activity in the different cell types in the SVZ of euthyroid and hypothyroid mice...
November 2017: Molecular Metabolism
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