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https://www.readbyqxmd.com/read/28732241/generation-of-skeletal-myogenic-progenitors-from-human-pluripotent-stem-cells-using-non-viral-delivery-of-minicircle-dna
#1
Jaemin Kim, Vanessa K P Oliveira, Ami Yamamoto, Rita C R Perlingeiro
Currently, the most efficient and promising approach for generating large numbers of engraftable human skeletal myogenic progenitors from pluripotent stem cells requires the conditional in vitro overexpression of PAX7 using lentiviral vectors. Because a non-integrating approach would be preferable to eliminate or minimize the risk associated with random genomic integration, here we investigate whether transient expression of PAX7 using minicircle DNA would enable the generation of functional pluripotent stem cell-derived myogenic progenitors, equivalent to those generated by lentivirus...
July 12, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28732240/constitutive-transgene-expression-of-stem-cell-antigen-1-in-the-hair-follicle-alters-the-sensitivity-to-tumor-formation-and-progression
#2
Rikke Christensen, David M Owens, Annette C Füchtbauer, Anders Gunnarsson, Mette Ramsing, Ernst-Martin Füchtbauer, Uffe Birk Jensen
The cell surface protein Stem Cell Antigen-1 (Sca-1) marks stem or progenitor cells in several murine tissues and is normally upregulated during cancer development. Although the specific function of Sca-1 remains unknown, Sca-1 seems to play a role in proliferation, differentiation and cell migration in a number of tissues. In the skin epithelium, Sca-1 is highly expressed in the interfollicular epidermis but is absent in most compartments of the hair follicle; however, the function of Sca-1 in the skin has not been investigated...
July 8, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28732065/direct-targets-of-pstat5-signalling-in-erythropoiesis
#3
Kevin R Gillinder, Hugh Tuckey, Charles C Bell, Graham W Magor, Stephen Huang, Melissa D Ilsley, Andrew C Perkins
Erythropoietin (EPO) acts through the dimeric erythropoietin receptor to stimulate proliferation, survival, differentiation and enucleation of erythroid progenitor cells. We undertook two complimentary approaches to find EPO-dependent pSTAT5 target genes in murine erythroid cells: RNA-seq of newly transcribed (4sU-labelled) RNA, and ChIP-seq for pSTAT5 30 minutes after EPO stimulation. We found 302 pSTAT5-occupied sites: ~15% of these reside in promoters while the rest reside within intronic enhancers or intergenic regions, some >100kb from the nearest TSS...
2017: PloS One
https://www.readbyqxmd.com/read/28732051/cd4-is-expressed-on-a-heterogeneous-subset-of-hematopoietic-progenitors-which-persistently-harbor-cxcr4-and-ccr5-tropic-hiv-proviral-genomes-in-vivo
#4
Nadia T Sebastian, Thomas D Zaikos, Valeri Terry, Frances Taschuk, Lucy A McNamara, Adewunmi Onafuwa-Nuga, Ryan Yucha, Robert A J Signer, James Riddell, Dale Bixby, Norman Markowitz, Sean J Morrison, Kathleen L Collins
Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28732024/4-nitrophenylsulfonyl-piperazines-mitigate-radiation-damage-to-multiple-tissues
#5
Ewa D Micewicz, Kwanghee Kim, Keisuke S Iwamoto, Josephine A Ratikan, Genhong Cheng, Gayle M Boxx, Robert D Damoiseaux, Julian P Whitelegge, Piotr Ruchala, Christine Nguyen, Prabhat Purbey, Joseph Loo, Gang Deng, Michael E Jung, James W Sayre, Andrew J Norris, Dörthe Schaue, William H McBride
Our ability to use ionizing radiation as an energy source, as a therapeutic agent, and, unfortunately, as a weapon, has evolved tremendously over the past 120 years, yet our tool box to handle the consequences of accidental and unwanted radiation exposure remains very limited. We have identified a novel group of small molecule compounds with a 4-nitrophenylsulfonamide (NPS) backbone in common that dramatically decrease mortality from the hematopoietic acute radiation syndrome (hARS). The group emerged from an in vitro high throughput screen (HTS) for inhibitors of radiation-induced apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28731612/mesoderm-lineage-3d-tissue-constructs-are-produced-at-large-scale-in-a-3d-stem-cell-bioprocess
#6
Jae Min Cha, Athanasios Mantalaris, Sunyoung Jung, Yurim Ji, Oh Young Bang, Hojae Bae
Various studies have presented different approaches to direct pluripotent stem cell differentiation such as applying defined sets of exogenous biochemical signals and genetic/epigenetic modifications. Although differentiation to target lineages was successfully regulated, such conventional methods are often complicated, laborious, and not cost-effective to be employed to the large-scale production of 3D stem cell-based tissue constructs. In this study, we developed a 3D-culture platform that could realize the large-scale production of mesoderm lineage tissue constructs from embryonic stem cells (ESCs)...
July 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28731527/mechanotransduction-effects-on-endothelial-cell-proliferation-via-cd31-and-vegfr2-implications-for-immunomagnetic-separation
#7
Kalpesh D Mahajan, Gauri M Nabar, Wei Xue, Mirela Anghelina, Nicanor Moldovan, Jeffrey Chalmers, Jessica Winter
Immunomagnetic separation is used to isolate circulating endothelial cells (ECs) and endothelial progenitor cells (EPCs) for diagnostics and tissue engineering. However, potentially detrimental changes in cell properties have been observed post-separation. Here, we studied the effect of mechanical force, which is naturally applied during immunomagnetic separation, on proliferation of human umbilical vein endothelial cells (HUVEC), kinase insert domain-positive receptor (KDR) cells, and peripheral blood mononuclear cells (PBMCs)...
July 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28731483/the-role-of-laminins-in-cartilaginous-tissues-from-development-to-regeneration
#8
Y Sun, T L Wang, W S Toh, M Pei
As a key molecule of the extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells) could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus) throughout several developmental stages...
July 21, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/28731447/chromatin-bound-oxidized-%C3%AE-synuclein-causes-strand-breaks-in-neuronal-genomes-in-in-vitro-models-of-parkinson-s-disease
#9
Velmarini Vasquez, Joy Mitra, Pavana M Hegde, Arvind Pandey, Shiladitya Sengupta, Sankar Mitra, K S Rao, Muralidhar L Hegde
Alpha-synuclein (α-Syn) overexpression and misfolding/aggregation in degenerating dopaminergic neurons have long been implicated in Parkinson's disease (PD). The neurotoxicity of α-Syn is enhanced by iron (Fe) and other pro-oxidant metals, leading to generation of reactive oxygen species in PD brain. Although α-Syn is predominantly localized in presynaptic nerve terminals, a small fraction exists in neuronal nuclei. However, the functional and/or pathological role of nuclear α-Syn is unclear. Following up on our earlier report that α-Syn directly binds DNA in vitro, here we confirm the nuclear localization and chromatin association of α-Syn in neurons using proximity ligation and chromatin immunoprecipitation analysis...
July 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28730859/molecular-targeting-of-inosine-5-monophosphate-dehydrogenase-by-ff-10501-promotes-erythropoiesis-via-ros-mapk-pathway
#10
Michiko Ichii, Kenji Oritani, Motohiko Murase, Kensuke Komatsu, Mao Yamazaki, Rie Kyoden, Nobuko Kito, Yusuke Nozaki, Motoki Saito, Hiroyuki Iwamura, Yuzuru Kanakura
One of the major symptoms of myelodysplastic syndromes (MDS) is severe cytopenia. Despite cytokine therapies, such as erythropoiesis-stimulating agents, many patients still require blood transfusions, and the development of new therapeutic approaches is needed. In this work, we studied the effects of the inosine-5'-monophosphate (IMP) dehydrogenase (IMPDH) inhibitor FF-10501 on erythropoiesis of human hematopoietic cells. Differentiation of K562 chronic myeloid leukemia cells to an erythroid lineage was promoted by FF-10501 in a dose-dependent manner...
July 21, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28730141/extracellular-vesicles-as-modulators-of-tumor-microenvironment-and-disease-progression-in-glioma
#11
REVIEW
Abir Mondal, Divya Kumari Singh, Suchismita Panda, Anjali Shiras
Diffuse gliomas are lethal tumors of the central nervous system (CNS) characterized by infiltrative growth, aggressive nature, and therapeutic resistance. The recent 2016 WHO classification for CNS tumors categorizes diffuse glioma into two major types that include IDH wild-type glioblastoma, which is the predominant type and IDH-mutant glioblastoma, which is less common and displays better prognosis. Recent studies suggest presence of a distinct cell population with stem cell features termed as glioma stem cells (GSCs) to be causal in driving tumor growth in glioblastoma...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28729817/ssr-marker-variations-in-brassica-species-provide-insight-into-the-origin-and-evolution-of-brassica-amphidiploids
#12
Ajay Kumar Thakur, Kunwar Harendra Singh, Lal Singh, Joghee Nanjundan, Yasin Jeshima Khan, Dhiraj Singh
BACKGROUND: Oilseed Brassica represents an important group of oilseed crops with a long history of evolution and cultivation. To understand the origin and evolution of Brassica amphidiploids, simple sequence repeat (SSR) markers were used to unravel genetic variations in three diploids and three amphidiploid Brassica species of U's triangle along with Eruca sativa as an outlier. RESULTS: Of 124 Brassica-derived SSR loci assayed, 100% cross-transferability was obtained for B...
2018: Hereditas
https://www.readbyqxmd.com/read/28729726/heart-regeneration-and-repair-after-myocardial-infarction-translational-opportunities-for-novel-therapeutics
#13
REVIEW
Thomas J Cahill, Robin P Choudhury, Paul R Riley
Current therapies for heart failure after myocardial infarction are limited and non-curative. Although regenerative approaches are receiving significant attention, clinical efforts that involve transplantation of presumed stem and progenitor cells have largely failed to deliver. Recent studies of endogenous heart regeneration in model organisms, such as zebrafish and neonatal mice, are yielding mechanistic insights into the roles of cardiomyocyte proliferation, resident stem cell niches, neovascularization, the immune system and the extracellular matrix...
July 21, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28729719/inhibition-of-tgf-%C3%AE-signaling-supports-high-proliferative-potential-of-diverse-p63-mouse-epithelial-progenitor-cells-in-vitro
#14
Daisuke Suzuki, Filipa Pinto, Makoto Senoo
Mouse models have been used to provide primary cells to study physiology and pathogenesis of epithelia. However, highly efficient simple approaches to propagate mouse primary epithelial cells remain challenging. Here, we show that pharmacological inhibition of TGF-β signaling enables long-term expansion of p63(+) epithelial progenitor cells in low Ca(2+) media without the need of progenitor cell-purification steps or support by a feeder cell layer. We find that TGF-β signaling is operative in mouse primary keratinocytes in conventional cultures as determined by the nuclear Smad2/3 localization...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729666/expansion-of-human-midbrain-floor-plate-progenitors-from-induced-pluripotent-stem-cells-increases-dopaminergic-neuron-differentiation-potential
#15
Stefania Fedele, Ginetta Collo, Katharina Behr, Josef Bischofberger, Stephan Müller, Tilo Kunath, Klaus Christensen, Anna Lisa Gündner, Martin Graf, Ravi Jagasia, Verdon Taylor
Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729654/cryopreservation-protocol-for-human-biliary-tree-stem-progenitors-hepatic-and-pancreatic-precursors
#16
Lorenzo Nevi, Vincenzo Cardinale, Guido Carpino, Daniele Costantini, Sabina Di Matteo, Alfredo Cantafora, Fabio Melandro, Roberto Brunelli, Carlo Bastianelli, Camilla Aliberti, Marco Monti, Daniela Bosco, Pasquale Bartolomeo Berloco, Pierluigi Benedetti Panici, Lola Reid, Eugenio Gaudio, Domenico Alvaro
Human biliary tree stem/progenitor cells (hBTSCs) are being used for cell therapies of patients with liver cirrhosis. A cryopreservation method was established to optimize sourcing of hBTSCs for these clinical programs and that comprises serum-free Kubota's Medium (KM) supplemented with 10% dimethyl sulfoxide (DMSO), 15% human serum albumin (HSA) and 0.1% hyaluronans. Cryopreserved versus freshly isolated hBTSCs were similar in vitro with respect to self-replication, stemness traits, and multipotency. They were able to differentiate to functional hepatocytes,cholangiocytes or pancreatic islets, yielding similar levels of secretion of albumin or of glucose-inducible levels of insulin...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729432/tropomodulin1-controls-erythroblast-enucleation-via-regulation-of-f-actin-in-the-enucleosome
#17
Roberta B Nowak, Julien Papoin, David S Gokhin, Carla Casu, Stefano Rivella, Jeffrey M Lipton, Lionel Blanc, Velia M Fowler
Biogenesis of mammalian red blood cells requires nuclear expulsion by orthochromatic erythoblasts late in terminal differentiation (enucleation), but the mechanism is largely unexplained. Here, we employed high resolution confocal microscopy to analyze nuclear morphology and F-actin rearrangements during the initiation, progression and completion of mouse and human erythroblast enucleation in vivo Mouse erythroblast nuclei acquire a dumbbell-shaped morphology during enucleation, while human bone marrow erythroblast nuclei unexpectedly retain their spherical morphology...
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28729363/brg1-brahma-related-gene-1-promotes-endothelial-mrtf-transcription-to-establish-embryonic-capillary-integrity
#18
Matthew T Menendez, E-Ching Ong, Brian T Shepherd, Vijay Muthukumar, Robert Silasi-Mansat, Florea Lupu, Courtney T Griffin
OBJECTIVE: The chromatin remodeling enzyme BRG1 (brahma-related gene 1) transcriptionally regulates target genes important for early blood vessel development and primitive hematopoiesis. However, because Brg1 deletion in vascular progenitor cells results in lethal anemia by embryonic day 10.5 (E10.5), roles for BRG1 in embryonic vascular development after midgestation are unknown. In this study, we sought to determine whether endothelial cell BRG1 regulates genes important for vascular development or maintenance later in embryonic development...
July 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28729300/rapamycin-is-highly-effective-in-murine-models-of-immune-mediated-bone-marrow-failure
#19
Xingmin Feng, Zenghua Lin, Wanling Sun, Maile K Hollinger, Marie J Desierto, Keyvan Keyvanfar, Daniela Malide, Pawel Muranski, Jichun Chen, Neal S Young
Acquired aplastic anemia, the prototypical bone marrow failure disease, is characterized by pancytopenia and marrow hypoplasia. Most aplastic anemia patients respond to immunosuppressive therapy, usually as anti-thymocyte globulin and cyclosporine, but some relapse on cyclosporine withdrawal or require long-term administration of cyclosporine to maintain blood counts. In the current study, we tested efficacy of rapamycin as a new or alternative treatment in mouse models of immune-mediated bone marrow failure...
July 20, 2017: Haematologica
https://www.readbyqxmd.com/read/28729299/notch2-blockade-enhances-hematopoietic-stem-cell-mobilization-and-homing
#20
Weihuan Wang, Shuiliang Yu, Jay Myers, Yiwei Wang, William W Xin, Marwah Alkabri, Alison W Xin, Ming Li, Alex Y Huang, Wei Xin, Christian W Siebel, Hillard M Lazarus, Lan Zhou
Despite use of newer approaches, some patients being considered for autologous hematopoietic cell transplantation may mobilize limited numbers of hematopoietic progenitor cells into blood, precluding use of the procedure, or being placed at increased risk for complications due to slow hematopoietic reconstitution. Developing more efficacious hematopoietic progenitor cell mobilization regimens and strategies may enhance the mobilization process and improve patient outcome. Although Notch signaling is dispensable for homeostasis of adult hematopoietic stem cells, Notch-ligand adhesive interaction maintains hematopoietic stem cell quiescence and niche retention...
July 20, 2017: Haematologica
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