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Reprogramation

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https://www.readbyqxmd.com/read/27936464/refractory-testicular-germ-cell-tumors-are-highly-sensitive-to-the-second-generation-dna-methylation-inhibitor-guadecitabine
#1
Costantine Albany, Mary P Hever-Jardine, Katherine M von Herrmann, Christina Y Yim, Janice Tam, Joshua M Warzecha, Leah Shin, Sarah E Bock, Brian S Curran, Aneeq S Chaudhry, Fred Kim, George E Sandusky, Pietro Taverna, Sarah J Freemantle, Brock C Christensen, Lawrence H Einhorn, Michael J Spinella
Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer...
December 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27935336/rrx-001-a-systemically-non-toxic-m2-to-m1-macrophage-stimulating-and-prosensitizing-agent-in-phase-ii-clinical-trials
#2
Bryan Oronsky, Ramasamy Paulmurugan, Kira Foygel, Jan Scicinski, Susan J Knox, Donna Peehl, Hongjuan Zhao, Shoucheng Ning, Pedro Cabrales, Thomas A Summers, Tony R Reid, William L Fitch, Michelle M Kim, Jane B Trepel, Min-Jung Lee, Santosh Kesari, Nacer D Abrouk, Regina M Day, Arnold Oronsky, Carolyn M Ray, Corey A Carter
According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: 1) self-sufficiency in growth signals, 2) insensitivity to growth-inhibitory signals, 3) evasion of programmed cell death, 4) limitless replicative potential, 5) sustained angiogenesis, and 6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes...
December 9, 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27934604/generation-of-induced-pluripotent-stem-cells-ipscs-stably-expressing-crispr-based-synergistic-activation-mediator-sam
#3
Kai Xiong, Yan Zhou, Poul Hyttel, Lars Bolund, Kristine Karla Freude, Yonglun Luo
Human fibroblasts were engineered to express the CRISPR-based synergistic activation mediator (SAM) complex: dCas9-VP64 and MS2-P65-HSF1. Two induced pluripotent stem cells (iPSCs) clones expressing SAM were established by transducing these fibroblasts with lentivirus expressing OCT4, SOX2, KLF4 and C-MYC. We have validated that the reprogramming cassette is silenced in the SAM iPSC clones. Expression of pluripotency genes (OCT4, SOX2, LIN28A, NANOG, GDF3, SSEA4, and TRA-1-60), differentiation potential to all three germ layers, and normal karyotypes are validated...
November 17, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934603/generation-and-characterization-of-an-induced-pluripotent-stem-cell-ipsc-line-from-a-patient-with-clozapine-resistant-schizophrenia
#4
Fabio Marsoner, Matteo Marcatili, Thodoris Karnavas, Daniele Bottai, Armando D'Agostino, Silvio Scarone, Luciano Conti
Peripheral Blood Mononuclear Cells (PBMCs) were collected from a patient with clozapine-resistant (also known as "super-refractory") Schizophrenia. iPSCs were established with a non-integrating Sendai virus-based reprogramming system. A footprint-free hiPSC line was characterized to express the main endogenous pluripotency markers and to retain a normal karyotype. Cells showed pluripotency competency by giving rise to progeny of differentiated cells belonging to the three germ layers. This hiPSC line represents a valuable tool to obtain mature, pathology-relevant neuronal populations in vitro that are suitable to investigate the molecular background of the schizophrenic disorder and the resultant patients' response to treatments...
November 10, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934602/generation-of-human-ipscs-from-urine-derived-cells-of-a-patient-with-a-novel-homozygous-pai-1-mutation
#5
Muhammad Zeeshan Afzal, Melanie Gartz, Ekaterina A Klyachko, Sadiya Sana Khan, Sanjiv J Shah, Sweta Gupta, Amy D Shapiro, Douglas E Vaughan, Jennifer L Strande
We have generated a human induced pluripotent stem cell (iPSC) line under feeder-free culture conditions using the urine derived cells (UCs) collected from subject with a novel homozygous Plasminogen Activator Inhibitor-1 (PAI-1 null) mutation. The Sendai virus (SeV) vector encoding pluripotent Yamanaka transcription factors was used at a low multiplicity of infection to reprogram the PAI-1 UCs.
November 9, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934596/establishment-of-an-induced-pluripotent-stem-cell-ipsc-line-from-a-patient-with-clozapine-responder-schizophrenia
#6
Matteo Marcatili, Fabio Marsoner, Armando D'Agostino, Thodoris Karnavas, Daniele Bottai, Silvio Scarone, Luciano Conti
Peripheral blood mononuclear cells (PBMCs) were collected from a patient with treatment-refractory Schizophrenia who presented an exceptional clinical response to Clozapine. iPSC lines were established with a non-integrating reprogramming system based on Sendai virus. A footprint-free hiPSC line was characterized to confirm the expression of the main endogenous pluripotency markers and have a regular karyotype. Pluripotency was confirmed by differentiation into cells belonging to the three germ layers. This hiPSC line represents a valuable tool to study the molecular, biochemical and electrophysiological properties of mature neuronal populations belonging to Clozapine responder patients with a severe form of Schizophrenia...
November 9, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934594/establishment-of-induced-pluripotent-stem-cell-ipsc-line-from-55-year-old-male-patient-with-hemorrhagic-moyamoya-disease
#7
Marina Cardano, Fabio Marsoner, Matteo Marcatili, Thodoris Karnavas, Jacopo Zasso, Luigi Andrea Lanterna, Luciano Conti
Peripheral blood mononuclear cells (PBMCs) were collected from 55-year old male patient with a confirmed diagnosis of hemorrhagic Moyamoya disease (MMD). PBMCs were reprogrammed using Sendai virus particles delivering the four Yamanaka factors. A footprint-free hiPSC line was characterized by the expression of pluripotency markers and a normal karyotype. These cells were able to give rise to Embryoid Bodies and to a progeny of differentiated cells belonging to the 3 germ layers. This hiPSC line represents a suitable tool for modelling in vitro MMD disease to investigate the cellular mechanisms underlying the occurrence of this pathology...
November 9, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934593/establishment-of-induced-pluripotent-stem-cell-ipsc-line-from-an-8-year-old-female-patient-with-ischemic-moyamoya-disease
#8
Marina Cardano, Fabio Marsoner, Jacopo Zasso, Matteo Marcatili, Thodoris Karnavas, Luigi Andrea Lanterna, Luciano Conti
Peripheral blood mononuclear cells (PBMCs) were collected from an 8-year old female patient affected by ischemic Moyamoya disease (MMD). Patient's PBMCs were reprogrammed using Sendai virus particles delivering the four Yamanaka factors. The footprint free hiPSC line expressed the major pluripotency markers and exhibited a normal karyotype. Cells were competent to give rise to progeny of differentiated cells belonging to the 3 germ layers. This hiPSC line represents a good tool to in vitro model MMD in order to shed light on the cellular and molecular mechanisms responsible for the occurrence of this syndrome...
November 5, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934592/generation-of-merrf-patient-derived-induced-pluripotent-stem-cell-line-imerrf-c7
#9
Dong Liang, Huanran Hu, Tianhui Xu, Yan Wang, Ping Hu, Zhengfeng Xu
Human iPSC line iMERRF-C7 was generated from PBMCs of a patient with mitochondrial disorder MERRF. Using Sendai virus, the reprogramming factors Oct3/4, Sox2, Klf4, and cMyc were delivered non-integratively. The resulting iPSCs expressed pluripotency markers, could differentiate into the three germ layers in vivo, had normal genomic structure, and retained the disease-causing m.8344 mutation with similar heteroplasmic level.
November 5, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934591/generation-of-a-human-induced-pluripotent-stem-cell-ipsc-line-from-a-bernard-soulier-syndrome-patient-with-the-mutation-p-asn45ser-in-the-gpix-gene
#10
Lourdes Lopez-Onieva, Candela Machuca, Mar Lamolda, Rosa Montes, Maria Luisa Lozano, Vicente Vicente, José Rivera, Verónica Ramos-Mejía, Pedro J Real
Bernard Soulier Syndrome (BSS) is an inherited rare platelet disorder characterized by mutations in the platelet glycoprotein complex GPIb-IX-V. We generated an induced pluripotent stem cell (iPSC) line from a BSS patient with a mutation p.Asn45Ser in the GPIX locus (BSS2-PBMC-iPS4F24). Peripheral blood mononuclear cells were reprogrammed using non-integrative viral transduction. Characterization of BSS2-PBMC-iPS4F24 included mutational analysis of GPIX locus, analysis of conventional pluripotency-associated factors at mRNA and protein level and in vitro and in vivo differentiation studies...
November 8, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934589/characterization-of-ipscs-derived-from-dermal-fibroblasts-from-a-healthy-19year-old-female
#11
Marie-Ann Kawala, Martina Bohndorf, Nina Graffmann, Wasco Wruck, Kurt Zatloukal, James Adjaye
Primary fibroblasts from a healthy 19years old female were reprogrammed by transduction of retroviruses OCT4, SOX2, c-MYC and KLF4. iPSCs were characterized by immunocytochemistry, embryonic body-formation, DNA-fingerprint and karyotype analysis and comparative transcriptome analyses with the human embryonic stem cell line H1 revealed a Pearsons correlation coefficient of 0.8952.
October 19, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934587/generation-of-an-ipsc-line-from-a-patient-with-tyrosine-hydroxylase-th-deficiency-th-1-ipsc
#12
Sabine Jung-Klawitter, Nenad Blau, Attila Sebe, Juliane Ebersold, Gudrun Göhring, Thomas Opladen
Fibroblasts from a male patient with compound heterozygous variants in the tyrosine hydroxylase gene (TH; OMIM: 191290; c.[385-C>T]; [692-G>C]/p.[R129*]; [R231P]), the rate-limiting enzyme for dopamine synthesis, were reprogrammed to iPSCs using episomal reprogramming delivering the reprogramming factors Oct3/4, Sox2, L-Myc, Lin28, Klf4 and p53 shRNA Okita et al. (2011). Pluripotency of TH-1 iPSC was verified by immunohistochemistry and RT-PCR analysis. Cells exhibited a normal karyotype and differentiated spontaneously into the 3 germ layers in vitro...
October 26, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27933223/epigenetic-editing-on-the-verge-of-reprogramming-gene-expression-at-will
#13
REVIEW
David Cano-Rodriguez, Marianne G Rots
Genome targeting has quickly developed as one of the most promising fields in science. By using programmable DNA-binding platforms and nucleases, scientists are now able to accurately edit the genome. These DNA-binding tools have recently also been applied to engineer the epigenome for gene expression modulation. Such epigenetic editing constructs have firmly demonstrated the causal role of epigenetics in instructing gene expression. Another focus of epigenome engineering is to understand the order of events of chromatin remodeling in gene expression regulation...
2016: Current Genetic Medicine Reports
https://www.readbyqxmd.com/read/27933082/rna-seq-transcriptome-response-of-flax-linum-usitatissimum-l-to-the-pathogenic-fungus-fusarium-oxysporum-f-sp-lini
#14
Leonardo Galindo-González, Michael K Deyholos
Fusarium oxysporum f. sp. lini is a hemibiotrophic fungus that causes wilt in flax. Along with rust, fusarium wilt has become an important factor in flax production worldwide. Resistant flax cultivars have been used to manage the disease, but the resistance varies, depending on the interactions between specific cultivars and isolates of the pathogen. This interaction has a strong molecular basis, but no genomic information is available on how the plant responds to attempted infection, to inform breeding programs on potential candidate genes to evaluate or improve resistance across cultivars...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27932467/reprogramming-of-cardiac-repolarization-notch-signals-a-potential-role-for-epigenetic-transcriptional-events
#15
EDITORIAL
Justus M Anumonwo
No abstract text is available yet for this article.
December 9, 2016: Circulation Research
https://www.readbyqxmd.com/read/27932444/activin-promotes-skin-carcinogenesis-by-attraction-and-reprogramming-of-macrophages
#16
Maria Antsiferova, Aleksandra Piwko-Czuchra, Michael Cangkrama, Mateusz Wietecha, Dilara Sahin, Katharina Birkner, Valerie C Amann, Mitchell Levesque, Daniel Hohl, Reinhard Dummer, Sabine Werner
Activin has emerged as an important player in different types of cancer, but the underlying mechanisms are largely unknown. We show here that activin overexpression is an early event in murine and human skin tumorigenesis. This is functionally important, since activin promoted skin tumorigenesis in mice induced by the human papillomavirus 8 oncogenes. This was accompanied by depletion of epidermal γδ T cells and accumulation of regulatory T cells. Most importantly, activin increased the number of skin macrophages via attraction of blood monocytes, which was prevented by depletion of CCR2-positive monocytes...
December 8, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27932417/molecular-pathways-the-necrosome-a-target-for-cancer-therapy
#17
Lena Seifert, George Miller
Necroptosis is a caspase 8-independent cell death that requires co-activation of receptor-interacting protein (RIP) 1 and RIP 3 kinases. The necrosome is a complex consisting of RIP1, RIP3 and Fas-associated protein with death domain (FADD) leading to activation of the pseudokinase mixed lineage kinase like (MLKL) followed by a rapid plasma membrane rupture and inflammatory response through the release of damage-associated molecular patterns (DAMPs) and cytokines. The necrosome has been shown to be relevant in multiple tumor types, including pancreatic adenocarcinoma, melanoma and several hematological malignancies...
December 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27932312/targeted-apoptosis-of-parietal-cells-is-insufficient-to-induce-metaplasia-in-stomach
#18
Joseph Burclaff, Luciana H Osaki, Dengqun Liu, James R Goldenring, Jason C Mills
Parietal cell atrophy is considered to cause metaplasia in the stomach. We developed mice that express the diphtheria toxin receptor specifically in parietal cells to induce their death, and found this to increase proliferation in the normal stem cell zone and neck but not to cause metaplastic reprogramming of chief cells. Furthermore, the metaplasia-inducing agents tamoxifen or DMP-777 still induced metaplasia even following previous destruction of parietal cells by diphtheria toxin. Atrophy of parietal cells alone is therefore not sufficient to induce metaplasia-completion of metaplastic reprogramming of chief cells requires mechanisms beyond parietal cell injury or death...
December 5, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27932276/the-why-and-how-of-amino-acid-analytics-in-cancer-diagnostics-and-therapy
#19
REVIEW
Friederike Manig, Konstantin Kuhne, Cläre von Neubeck, Uwe Schwarzenbolz, Zhanru Yu, Benedikt M Kessler, Jens Pietzsch, Leoni A Kunz-Schughart
Pathological alterations in cell functions are frequently accompanied by metabolic reprogramming including modifications in amino acid metabolism. Amino acid detection is thus integral to the diagnosis of many hereditary metabolic diseases. The development of malignant diseases as metabolic disorders comes along with a complex dysregulation of genetic and epigenetic factors affecting metabolic enzymes. Cancer cells might transiently or permanently become auxotrophic for non-essential or semi-essential amino acids such as asparagine or arginine...
December 5, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27931510/generation-of-equine-induced-pluripotent-stem-cells-and-analysis-of-their-therapeutic-potential-for-muscle-injuries
#20
Eun-Mi Lee, Ah-Young Kim, Eun-Joo Lee, Jin-Kyu Park, Se-Il Park, Ssang-Goo Cho, Hong Kyun Kim, Shin-Yoon Kim, Kyu-Shik Jeong
Horse health has become a major concern with the expansion of horse-related industries and sports; the importance of healthy muscles for horse performance and daily activities is undisputed. Here we generated equine-induced pluripotent stem cells (E-iPSCs) by reprogramming equine adipose-derived stem cells (E-ADSCs) into iPSCs using a polycistronic lentiviral vector encoding four transcription factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and then examined their pluripotent characteristics. Subsequently, established E-iPSCs were transplanted into muscle-injured Rag/mdx mice...
November 2016: Cell Transplantation
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