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https://www.readbyqxmd.com/read/28817722/nicotinamide-alone-accelerates-the-conversion-of-mouse-embryonic-stem-cells-into-mature-neuronal-populations
#1
Síle M Griffin, Mark R Pickard, Rowan P Orme, Clive P Hawkins, Adrian C Williams, Rosemary A Fricker
INTRODUCTION: Vitamin B3 has been shown to play an important role during embryogenesis. Specifically, there is growing evidence that nicotinamide, the biologically active form of vitamin B3, plays a critical role as a morphogen in the differentiation of stem cells to mature cell phenotypes, including those of the central nervous system (CNS). Detailed knowledge of the action of small molecules during neuronal differentiation is not only critical for uncovering mechanisms underlying lineage-specification, but also to establish more effective differentiation protocols to obtain clinically relevant cells for regenerative therapies for neurodegenerative conditions such as Huntington's disease (HD)...
2017: PloS One
https://www.readbyqxmd.com/read/28815565/generation-of-animal-form-by-the-chordin-tolloid-bmp-gradient-100%C3%A2-years-after-d-arcy-thompson
#2
Edward M De Robertis, Yuki Moriyama, Gabriele Colozza
The classic book "On Growth and Form" by naturalist D'Arcy Thompson was published 100 years ago. To celebrate this landmark, we present experiments in the Xenopus embryo that provide a framework for understanding how simple, quantitative transformations of a morphogen gradient might have affected evolution and morphological diversity of organisms. D'Arcy Thompson proposed that different morphologies might be generated by modifying physical parameters in an underlying system of Cartesian coordinates that pre-existed in Nature and arose during evolutionary history...
August 16, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28815333/comparison-of-different-culture-conditions-for-smooth-muscle-cell-differentiation-of-human-umbilical-cord-vein-cd146-perivascular-cells
#3
Beyza Gökçinar-Yagci, Betül Çelebi-Saltik
Pericytes are CD146+ perivascular cells (PCs) that have multipotential differentiation capacity as mesenchymal stem cells. Beside their crucial roles in vascular development and blood flow regulation, they have ability to differentiate into vascular cell types in vivo. These properties make pericytes preferred cells in the field of vascular tissue engineering. Culture medium for in vitro differentiation of pericytes to vascular smooth muscle cells (SMCs) has not been defined yet. The aim of this study is to try different culture media for SMC differentiation of CD146+ PCs...
August 16, 2017: Cell and Tissue Banking
https://www.readbyqxmd.com/read/28806852/generation-of-oligodendrogenic-spinal-neural-progenitor-cells-from-human-induced-pluripotent-stem-cells
#4
Mohamad Khazaei, Christopher S Ahuja, Michael G Fehlings
This unit describes protocols for the efficient generation of oligodendrogenic neural progenitor cells (o-NPCs) from human induced pluripotent stem cells (hiPSCs). Specifically, detailed methods are provided for the maintenance and differentiation of hiPSCs, human induced pluripotent stem cell-derived neural progenitor cells (hiPS-NPCs), and human induced pluripotent stem cell-oligodendrogenic neural progenitor cells (hiPSC-o-NPCs) with the final products being suitable for in vitro experimentation or in vivo transplantation...
August 14, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28806146/three-dimensional-bioprinting-of-polycaprolactone-reinforced-gene-activated-bioinks-for-bone-tissue-engineering
#5
Gráinne M Cunniffe, Tomas Gonzalez-Fernandez, Andrew Daly, Binulal N Sathy, Oju Jeon, Eben Alsberg, Daniel J Kelly
Regeneration of complex bone defects remains a significant clinical challenge. Multi-tool biofabrication has permitted the combination of various biomaterials to create multifaceted composites with tailorable mechanical properties and spatially controlled biological function. In this study we sought to use bioprinting to engineer nonviral gene activated constructs reinforced by polymeric micro-filaments. A gene activated bioink was developed using RGD-γ-irradiated alginate and nano-hydroxyapatite (nHA) complexed to plasmid DNA (pDNA)...
August 14, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28780023/shared-acvr1-mutations-in-fop-and-dipg-opportunities-and-challenges-in-extending-biological-and-clinical-implications-across-rare-diseases
#6
Harry J Han, Payal Jain, Adam C Resnick
Gain-of-function mutations in the Type I Bone Morphogenic Protein (BMP) receptor ACVR1 have been identified in two diseases: Fibrodysplasia Ossificans Progressiva (FOP), a rare autosomal dominant disorder characterized by genetically driven heterotopic ossification, and in 20-25% of Diffuse Intrinsic Pontine Gliomas (DIPGs), a pediatric brain tumor with no effective therapies and dismal median survival. While the ACVR1 mutation is causal for FOP, its role in DIPG tumor biology remains under active investigation...
August 2, 2017: Bone
https://www.readbyqxmd.com/read/28777920/complications-associated-with-the-use-of-recombinant-human-bone-morphogenic-protein-2-in-ridge-augmentation-a-case-report
#7
Panagiotis Dragonas, Charles Palin, Saba Khan, Praveen Gajendrareddy, Whitney Weiner
This case report aims to describe in detail a complication associated with resorption of regenerated bone following implant placement and ridge augmentation using rhBMP-2 in combination with allograft and xenograft. Bilateral maxillary sinus and ridge augmentation procedures were completed using rhBMP-2 combined with allograft and xenograft. Five months later, significant bone augmentation was achieved which allowed for the placement of 4 implants. Upon stage 2 surgery, significant dehiscence was noted in all implants...
August 4, 2017: Journal of Oral Implantology
https://www.readbyqxmd.com/read/28774557/fibroblast-growth-factor-21-plays-an-inhibitory-role-in-vascular-calcification-in-vitro-through-opg-rankl-system
#8
Fangying Cao, Xiaoxiao Liu, Xiangrong Cao, Shaoping Wang, Kun Fu, Yejing Zhao, Fang Shen, Jinghua Liu
Vascular calcification is prevalent and associated with adverse outcome without available therapy. The benefits of fibroblast growth factor (FGF)-21 on metabolism and atherosclerosis make it a promising therapeutic agent for vascular calcification. We investigated the effects of FGF21 on vascular smooth muscle cell (VSMC) calcification by culturing rat VSMCs in a calcifying medium for 9days. FGF21 markedly attenuated mineral deposition and apoptosis at the indicated time points. In the presence of FGF21, the expression levels of osteoblastic protein including bone morphogenic protein-2, alkaline phosphatase(ALP), runt-related transcription factor(RUNX)-2 and nuclear factor-kappa B ligand (RANKL) were down-regulated, whereas the expression of osteoprotegerin (OPG) increased...
July 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28771710/brain-endothelial-cells-induce-astrocytic-expression-of-the-glutamate-transporter-glt-1-by-a-notch-dependent-mechanism
#9
Meredith L Lee, Zila Martinez-Lozada, Elizabeth N Krizman, Michael B Robinson
Neuron-secreted factors induce astrocytic expression of the glutamate transporter, GLT-1 (EAAT2). In addition to their elaborate anatomic relationships with neurons, astrocytes also have processes that extend to and envelop the vasculature. Although previous studies have demonstrated that brain endothelia contribute to astrocyte differentiation and maturation, the effects of brain endothelia on astrocytic expression of GLT-1 have not been examined. In the present study, we tested the hypothesis that endothelia induce expression of GLT-1 by co-culturing astrocytes from mice that utilize non-coding elements of the GLT-1 gene to control expression reporter proteins with the mouse endothelial cell line, bEND...
August 3, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28768485/a-systematic-review-of-genetic-mutations-in-pulmonary-arterial-hypertension
#10
Gerardo Garcia-Rivas, Carlos Jerjes-Sánchez, David Rodriguez, José Garcia-Pelaez, Victor Trevino
BACKGROUND: Pulmonary arterial hypertension (PAH) is a group of vascular diseases that produce right ventricular dysfunction, heart failure syndrome, and death. Although the majority of patients appear idiopathic, accumulated research work combined with current sequencing technology show that many gene variants could be an important component of the disease. However, current guidelines, clinical practices, and available gene panels focus the diagnosis of PAH on a relatively low number of genes and variants associated with the bone morphogenic proteins and transforming Growth Factor-β pathways, such as the BMPR2, ACVRL1, CAV1, ENG, and SMAD9...
August 2, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28760810/morphogen-and-community-effects-determine-cell-fates-in-response-to-bmp4-signaling-in-human-embryonic-stem-cells
#11
Anastasiia Nemashkalo, Albert Ruzo, Idse Heemskerk, Aryeh Warmflash
Paracrine signals maintain developmental states and create cell-fate patterns in vivo, and influence differentiation outcomes in human embryonic stem cells (hESCs) in vitro. Systematic investigation of morphogen signaling is hampered by the difficulty of disentangling endogenous signaling from experimentally applied ligands. Here, we grow hESCs in micropatterned colonies of 1-8 cells ("μColonies") to quantitatively investigate paracrine signaling and the response to external stimuli. We examine BMP4-mediated differentiation in μColonies and standard culture conditions and find that in μColonies, above a threshold concentration, BMP4 gives rise to only a single cell fate, contrary to its role as a morphogen in other developmental systems...
July 31, 2017: Development
https://www.readbyqxmd.com/read/28760079/preparation-of-cell-aggregates-incorporating-gelatin-hydrogel-microspheres-containing-bone-morphogenic-protein-2-with-different-degradabilities
#12
Shuhei Tajima, Yasuhiko Tabata
The objective of this study is to evaluate the survival and functions of cells in cell aggregates incorporating gelatin hydrogel microspheres (GM) containing bone morphogenic protein-2 (BMP2). Gelatin was dehydrothermally crosslinked in a water-in-oil emulsion state at 140 °C for various time periods to prepare GM with different degradabilities. BMP2 was dropped onto the GM freeze dried, followed by leaving at 25 °C to obtain GM containing BMP2 (GM-BMP2). MC3T3-E1 cells were cultured with GM-BMP2 and GM in round U-bottom wells of 96-multiwell microplates which had been coated with poly (vinyl alcohol) (PVA), to allow to form cell aggregates containing GM-BMP2 and GM, respectively...
July 31, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28757170/the-deleterious-interplay-between-tumor-epithelia-and-stroma-in-cholangiocarcinoma
#13
REVIEW
Massimiliano Cadamuro, Tommaso Stecca, Simone Brivio, Valeria Mariotti, Romina Fiorotto, Carlo Spirli, Mario Strazzabosco, Luca Fabris
Prognosis of cholangiocarcinoma, a devastating liver epithelial malignancy characterized by early invasiveness, remains very dismal, though its incidence has been steadily increasing. Evidence is mounting that in cholangiocarcinoma, tumor epithelial cells establish an intricate web of mutual interactions with multiple stromal components, largely determining the pervasive behavior of the tumor. The main cellular components of the tumor microenvironment (i.e. myofibroblasts, macrophages, lymphatic endothelial cells), which has been recently termed as 'tumor reactive stroma', are recruited and activated by neoplastic cells, and in turn, deleteriously mold tumor behavior by releasing a huge variety of paracrine signals, including cyto/chemokines, growth factors, morphogens and proteinases...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28757164/surface-topography-guides-morphology-and-spatial-patterning-of-induced-pluripotent-stem-cell-colonies
#14
Giulio Abagnale, Antonio Sechi, Michael Steger, Qihui Zhou, Chao-Chung Kuo, Gülcan Aydin, Carmen Schalla, Gerhard Müller-Newen, Martin Zenke, Ivan G Costa, Patrick van Rijn, Arnold Gillner, Wolfgang Wagner
The relevance of topographic cues for commitment of induced pluripotent stem cells (iPSCs) is largely unknown. In this study, we demonstrate that groove-ridge structures with a periodicity in the submicrometer range induce elongation of iPSC colonies, guide the orientation of apical actin fibers, and direct the polarity of cell division. Elongation of iPSC colonies impacts also on their intrinsic molecular patterning, which seems to be orchestrated from the rim of the colonies. BMP4-induced differentiation is enhanced in elongated colonies, and the submicron grooves impact on the spatial modulation of YAP activity upon induction with this morphogen...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28754838/the-chromatin-remodeling-bap-complex-limits-tumor-promoting-activity-of-the-hippo-pathway-effector-yki-to-prevent-neoplastic-transformation-in-drosophila-epithelia
#15
Shilin Song, Héctor Herranz, Stephen M Cohen
SWI/SNF chromatin remodeling complexes are mutated in many human cancers. In this report we make use of a Drosophila genetic model for epithelial tumor formation to explore the tumor suppressive role of SWI/SNF complex proteins. Members of the BAP complex exhibit tumor suppressor activity in tissue overexpressing the Yorkie (Yki) proto-oncogene, but not in tissue overexpressing EGFR. The BAP complex has been reported to serve as a Yki-binding cofactor to support Yki target expression. However, we observed that depletion of BAP leads to ectopic expression of Yki targets both autonomously and non-autonomously, suggesting additional indirect effects...
July 28, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28754309/retinoic-acid-cyp26-and-drug-resistance-in-the-stem-cell-niche
#16
REVIEW
Salvador Alonso, Richard J Jones, Gabriel Ghiaur
The bone marrow niche is essential for hematopoietic stem cells to maintain lifelong blood production, by balancing their self-renewal and differentiation. Hematologic malignancies have a similar hierarchical organization to their normal counterparts, with rare populations of cancer stem cells that rely on the microenvironment to survive and propagate their differentiated malignant progenitor cells. Cancer cells alter their microenvironment to create a supportive niche where they endure chemotherapy, survive as minimal residual disease, and eventually prevail at relapse...
July 25, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28751413/long-term-outcomes-of-dasatinib-induced-pulmonary-arterial-hypertension-a-population-based-study
#17
Jason Weatherald, Marie-Camille Chaumais, Laurent Savale, Xavier Jaïs, Andrei Seferian, Matthieu Canuet, Hélène Bouvaist, Pascal Magro, Anne Bergeron, Christophe Guignabert, Olivier Sitbon, Gérald Simonneau, Marc Humbert, David Montani
This study aimed to describe the long-term outcomes of pulmonary arterial hypertension (PAH) induced by dasatinib.21 incident, right heart catheterisation-confirmed cases of dasatinib-induced PAH were identified from the French Pulmonary Hypertension Registry. Clinical and haemodynamic variables were compared from baseline to last follow-up (median (range) 24 (1-81) months).Median age was 52 years and 15 patients were female (71%). 19 patients received dasatinib for chronic myelogenous leukaemia for a median (range) duration of 42 (8-74) months before PAH diagnosis...
July 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28749339/pten-controls-glandular-morphogenesis-through-a-juxtamembrane-%C3%AE-arrestin1-arhgap21-scaffolding-complex
#18
Arman Javadi, Ravi K Deevi, Emma Evergren, Elodie Blondel-Tepaz, George S Baillie, Mark Gh Scott, Frederick Charles Campbell
PTEN controls three-dimensional (3D) glandular morphogenesis by coupling juxtamembrane signalling to mitotic spindle machinery. While molecular mechanisms remain unclear, PTEN interacts through its C2 membrane-binding domain with the scaffold protein β-Arrestin1. Because β-Arrestin1 binds and suppresses the Cdc42 GTPase-activating protein ARHGAP21, we hypothesize that PTEN controls Cdc42-dependent morphogenic processes through a β-Arrestin1-ARHGAP21 complex. Here we show that PTEN knockdown (KD) impairs β-Arrestin1 membrane localization, β-Arrestin1-ARHGAP21 interactions, Cdc42 activation, mitotic spindle orientation and 3D glandular morphogenesis...
July 27, 2017: ELife
https://www.readbyqxmd.com/read/28743979/expression-of-rmrp-rna-is-regulated-in-chondrocyte-hypertrophy-and-determines-chondrogenic-differentiation
#19
Mandy M F Steinbusch, Marjolein M J Caron, Don A M Surtel, Franziska Friedrich, Ekkehart Lausch, Ger J M Pruijn, Wouter Verhesen, Blanche L M Schroen, Lodewijk W van Rhijn, Bernhard Zabel, Tim J M Welting
Mutations in the RMRP-gene, encoding the lncRNA component of the RNase MRP complex, are the origin of cartilage-hair hypoplasia. Cartilage-hair hypoplasia is associated with severe dwarfism caused by impaired skeletal development. However, it is not clear why mutations in RMRP RNA lead to skeletal dysplasia. Since chondrogenic differentiation of the growth plate is required for development of long bones, we hypothesized that RMRP RNA plays a pivotal role in chondrogenic differentiation. Expression of Rmrp RNA and RNase MRP protein subunits was detected in the murine growth plate and during the course of chondrogenic differentiation of ATDC5 cultures, where Rmrp RNA expression was found to be correlated with chondrocyte hypertrophy...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28743798/essential-basal-cytonemes-take-up-hedgehog-in-the-drosophila-wing-imaginal-disc
#20
Weitao Chen, Hai Huang, Ryo Hatori, Thomas B Kornberg
Morphogen concentration gradients that extend across developmental fields form by dispersion from source cells. In the Drosophila wing disc, Hedgehog (Hh) produced by posterior compartment cells distributes in a concentration gradient to adjacent cells of the anterior compartment. We monitored Hh:GFP after pulsed expression and analyzed movements and co-localization of Hh, Patched (Ptc) and Smoothened (Smo) proteins tagged with GFP or mCherry and expressed at physiological levels from bacterial artificial chromosome transgenes...
July 25, 2017: Development
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