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https://www.readbyqxmd.com/read/29353456/in-vivo-transient-and-partial-cell-reprogramming-to-pluripotency-as-a-therapeutic-tool-for-neurodegenerative-diseases
#1
REVIEW
S Tamanini, G P Comi, S Corti
In theory, human diseases in which a specific cell type degenerates, such as neurodegenerative diseases, can be therapeutically addressed by replacement of the lost cells. The classical strategy for cell replacement is exogenous cell transplantation, but now, cell replacement can also be achieved with in situ reprogramming. Indeed, many of these disorders are age-dependent, and "rejuvenating" strategies based on cell epigenetic modifications are a possible approach to counteract disease progression. In this context, transient and/or partial reprogramming of adult somatic cells towards pluripotency can be a promising tool for neuroregeneration...
January 20, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29352121/efficient-differentiation-of-human-pluripotent-stem-cells-into-skeletal-muscle-cells-by-combining-rna-based-myod1-expression-and-pou5f1-silencing
#2
Tomohiko Akiyama, Saeko Sato, Nana Chikazawa-Nohtomi, Atsumi Soma, Hiromi Kimura, Shunichi Wakabayashi, Shigeru B H Ko, Minoru S H Ko
Direct generation of skeletal muscle cells from human pluripotent stem cells (hPSCs) would be beneficial for drug testing, drug discovery, and disease modelling in vitro. Here we show a rapid and robust method to induce myogenic differentiation of hPSCs by introducing mRNA encoding MYOD1 together with siRNA-mediated knockdown of POU5F1 (also known as OCT4 or OCT3/4). This integration-free approach generates functional skeletal myotubes with sarcomere-like structure and a fusion capacity in several days. The POU5F1 silencing facilitates MYOD1 recruitment to the target promoters, which results in the significant activation of myogenic genes in hPSCs...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29352035/using-mouse-transgenic-and-human-stem-cell-technologies-to-model-genetic-mutations-associated-with-schizophrenia-and-autism
#3
REVIEW
David St Clair, Mandy Johnstone
Solid progress has occurred over the last decade in our understanding of the molecular genetic basis of neurodevelopmental disorders, and of schizophrenia and autism in particular. Although the genetic architecture of both disorders is far more complex than previously imagined, many key loci have at last been identified. This has allowed in vivo and in vitro technologies to be refined to model specific high-penetrant genetic loci involved in both disorders. Using the DISC1/NDE1 and CYFIP1/EIF4E loci as exemplars, we explore the opportunities and challenges of using animal models and human-induced pluripotent stem cell technologies to further understand/treat and potentially reverse the worst consequences of these debilitating disorders...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29352015/sox2-is-required-for-olfactory-pit-formation-and-olfactory-neurogenesis-through-bmp-restriction-and-hes5-upregulation
#4
Tamilarasan K Panaliappan, Walter Wittmann, Vijay K Jidigam, Sara Mercurio, Jessica A Bertolini, Soufien Sghari, Raj Bose, Cedric Patthey, Silvia K Nicolis, Lena Gunhaga
The transcription factor Sox2 is necessary to maintain pluripotency of embryonic stem cells, and to regulate neural development. Neurogenesis in the vertebrate olfactory epithelium persists from embryonic stages through adulthood. The role Sox2 plays for the development of the olfactory epithelium and neurogenesis within has, however, not been determined. Here, by analysing Sox2 conditional knockout mouse embryos and chick embryos deprived of Sox2 in the olfactory epithelium using CRISPR-Cas9, we show that Sox2 activity is crucial for the induction of the neural progenitor gene Hes5 and for subsequent differentiation of the neuronal lineage...
January 19, 2018: Development
https://www.readbyqxmd.com/read/29351105/stem-cell-modeling-of-lipid-genetics
#5
Kiran Musunuru
PURPOSE OF REVIEW: To summarize recent advances with respect to the use of human pluripotent stem cells to study the genetics of blood lipid traits. RECENT FINDINGS: Human pluripotent stem cell models have been used to elucidate the mechanisms by which genes contribute to dyslipidemia, to discover new lipid-related DNA variants and genes, and to perform drug screens. SUMMARY: In addition to enabling a better understanding of the genetic basis of lipid metabolism, human pluripotent stem cells are identifying potential therapeutic targets as well as potential therapies...
January 17, 2018: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/29350802/cellular-reprogramming-a-new-way-to-understand-aging-mechanisms
#6
REVIEW
Burcu Yener Ilce, Umut Cagin, Acelya Yilmazer
Increased life expectancy, due to the rise in life quality and the decline in mortality rates, is leading to a society in which the population aged 60 and over is growing more rapidly than the entire population. Although various models and model organisms have been employed to investigate the mechanism of aging, induced pluripotent stem cells (iPSCs) are useful candidates to study human aging and age-related human diseases. This work discusses how iPSCs can be used as an alternative to the model organisms such as yeast, Caenorhabditis elegans, Drosophila melanogaster, or the mouse...
January 19, 2018: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/29350722/chemical-decontamination-of-ips-cell-derived-neural-cell-mixtures
#7
Di Mao, Xie Khim Watson Chung, Tomoko Andoh-Noda, Ying Qin, Shin-Ichi Sato, Yasushi Takemoto, Wado Akamatsu, Hideyuki Okano, Motonari Uesugi
This report describes the design and evaluation of phosphorylated 7-ethyl-10-hydroxycamptothecin (SN38-P), which selectively eliminates tumor-forming proliferative stem cells, including human induced pluripotent stem cells (hiPSCs) and neural stem cells, from iPSC-derived neural cell mixtures. Results of the present study demonstrate that simple phosphorylation of an anticancer drug can provide a safe, cost-effective, and chemically-defined tool for decontaminating hiPSC-derived neuron.
January 19, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29350613/fgf-mediated-mapk-and-pi3k-akt-signals-make-distinct-contributions-to-pluripotency-and-the-establishment-of-neural-crest
#8
Lauren Geary, Carole LaBonne
Early vertebrate embryos possess cells with the potential to generate all embryonic cell types. While this pluripotency is progressively lost as cells become lineage restricted, Neural Crest cells retain broad developmental potential. Here, we provide novel insights into signals essential for both pluripotency and neural crest formation in Xenopus. We show that FGF signaling controls a subset of genes expressed by pluripotent blastula cells, and find a striking switch in the signaling cascades activated by FGF signaling as cells lose pluripotency and commence lineage restriction...
January 19, 2018: ELife
https://www.readbyqxmd.com/read/29348566/phosphorylation-of-ulk1-by-ampk-is-essential-for-mouse-embryonic-stem-cell-self-renewal-and-pluripotency
#9
Jiaqi Gong, Haifeng Gu, Lin Zhao, Liang Wang, Pinglei Liu, Fuping Wang, Haoyu Xu, Tongbiao Zhao
Autophagy is a catabolic process to degrade both damaged organelles and aggregated proteins in somatic cells. We have recently identified that autophagy is an executor for mitochondrial homeostasis in embryonic stem cell (ESC), and thus contribute to stemness regulation. However, the regulatory and functional mechanisms of autophagy in ESC are still largely unknown. Here we have shown that activation of ULK1 by AMPK is essential for ESC self-renewal and pluripotency. Dysfunction of Ulk1 decreases the autophagic flux in ESC, leading to compromised self-renewal and pluripotency...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348408/nipbl-haploinsufficiency-reveals-a-constellation-of-transcriptome-disruptions-in-the-pluripotent-and-cardiac-states
#10
Jason A Mills, Pamela S Herrera, Maninder Kaur, Lanfranco Leo, Deborah McEldrew, Jesus A Tintos-Hernandez, Ramakrishnan Rajagopalan, Alyssa Gagne, Zhe Zhang, Xilma R Ortiz-Gonzalez, Ian D Krantz
Cornelia de Lange syndrome (CdLS) is a complex disorder with multiple structural and developmental defects caused by mutations in structural and regulatory proteins involved in the cohesin complex. NIPBL, a cohesin regulatory protein, has been identified as a critical protein responsible for the orchestration of transcriptomic regulatory networks necessary for embryonic development. Mutations in NIPBL are responsible for the majority of cases of CdLS. Through RNA-sequencing of human induced pluripotent stem cells and in vitro-derived cardiomyocytes, we identified hundreds of mRNAs, pseudogenes, and non-coding RNAs with altered expression in NIPBL+/- patient-derived cells...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348245/induced-pluripotent-stem-cells-derived-extracellular-vesicles-a-potential-therapy-for-cardiac-repair
#11
EDITORIAL
Venkata Naga Srikanth Garikipati, Raj Kishore
No abstract text is available yet for this article.
January 19, 2018: Circulation Research
https://www.readbyqxmd.com/read/29346426/proliferation-and-survival-of-human-amniotic-epithelial-cells-during-their-hepatic-differentiation
#12
Julieta L Maymó, Rodrigo Riedel, Antonio Pérez-Pérez, Marta Magatti, Bernardo Maskin, José Luis Dueñas, Ornella Parolini, Víctor Sánchez-Margalet, Cecilia L Varone
Stem cells derived from placental tissues are an attractive source of cells for regenerative medicine. Amniotic epithelial cells isolated from human amnion (hAECs) have desirable and competitive characteristics that make them stand out between other stem cells. They have the ability to differentiate toward all three germ layers, they are not tumorigenic and they have immunosuppressive properties. Although liver transplantation is the best way to treat acute and chronic hepatic failure patients, there are several obstacles...
2018: PloS One
https://www.readbyqxmd.com/read/29345024/being-pluripotent-bone-marrow-vsels-rather-than-hscs-have-the-potential-to-regenerate-other-adult-organs
#13
REVIEW
Deepa Bhartiya
Recent study by Deanne's group provides evidence that transplanted GFP positive bone marrow hematopoietic stem cells (HSCs) expressing CD45 do not regenerate the endometrium of irradiated mice. The results do not surprise us since global efforts to regenerate various organs by transplanting bone marrow (BM) mononuclear cells (presumably enriched for HSCs) have failed. HSCs can only regenerate/reconstitute BM as they are 'committed progenitors' that are specified from more primitive, CD45 negative stem cells...
January 18, 2018: Stem Cells
https://www.readbyqxmd.com/read/29345014/human-induced-pluripotent-stem-cell-models-of-retinitis-pigmentosa
#14
REVIEW
Ana Artero Castro, Dunja Lukovic, Pavla Jendelova, Slaven Erceg
Hereditary retinal dystrophies, specifically retinitis pigmentosa (RP) are clinically and genetically heterogeneous diseases affecting primarily retinal cells and retinal pigment epithelial (RPE) cells with blindness as a final outcome. Understanding the pathogenicity behind these diseases has been largely precluded by the unavailability of affected tissue from patients, large genetic heterogeneity and animal models that do not faithfully represent some human diseases. A landmark discovery of human induced pluripotent stem cells (hiPSC) permitted the derivation of patient-specific cells...
January 18, 2018: Stem Cells
https://www.readbyqxmd.com/read/29343702/analysis-of-mitochondrial-function-in-human-induced-pluripotent-stem-cells-from-patients-with-mitochondrial-diabetes-due-to-the-a3243g-mutation
#15
Masaki Matsubara, Hajime Kanda, Hiromi Imamura, Mayumi Inoue, Michio Noguchi, Kiminori Hosoda, Akira Kakizuka, Kazuwa Nakao
We previously established human induced pluripotent stem (iPS) cells in two diabetic patients from different families with the mitochondrial A3243G mutation and isolated isogenic iPS cell clones with either undetectable or high levels of the mutation in both patients. In the present study, we analyzed the mitochondrial functions of two mutation-undetectable and two mutation-high clones in each patient through four methods to assess complex I activity, mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343525/lack-of-remuscularization-following-transplantation-of-human-embryonic-stem-cell-derived-cardiovascular-progenitor-cells-in-infarcted-nonhuman-primates
#16
Keyang Zhu, Qiang Wu, Cheng Ni, Peng Zhang, Zhiwei Zhong, Yan Wu, Yingchao Wang, Yinchuan Xu, Minjian Kong, Haifeng Cheng, Zhihua Tao, Qian Yang, He Liang, Yun Jiang, Qingju Li, Jing Zhao, Jijun Huang, Fengjiang Zhang, Qi Chen, Yi Li, Jinghai Chen, Wei Zhu, Hong Yu, Jianyi Zhang, Huang-Tian Yang, Xinyang Hu, Jian'an Wang
Rationale: Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials. Objective: To clarify if hPSC-CVPCs can engraft for long time in the heart of primates after myo-cardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cy-closporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and Simulect in cynomolgous monkeys that had received intramyocardial injections of 1×107 EGFP-expressing hPSC-CVPCs after MI...
January 17, 2018: Circulation Research
https://www.readbyqxmd.com/read/29343174/small-molecules-for-neural-stem-cell-induction
#17
Donghui Liu, Nimshitha Pavathuparambil Abdul Manaph, Mohammed Al-Hawwas, Xin-Fu Zhou, Hong Liao
Generation of induced pluripotent stem cells (iPSCs) from other somatic cells has provided great hopes for transplantation therapies. However, these cells still cannot be used for clinical application due to the low reprogramming and differentiation efficiency beside the risk of mutagenesis and tumor formation. Compared to iPSCs, induced neural stem cells (iNSCs) are easier to terminally differentiate into neural cells and safer, thus, iNSCs hold more opportunities than iPSCs to treat neural diseases. On the other hand, recent studies have showed that small molecules (SMs) can dramatically improve the efficiency of reprogramming and SMs alone can even convert one kind of somatic cells into another, which is much safer and more effective than transcription factor-based methods...
January 17, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29342448/generation-of-induced-pluripotent-stem-cell-line-cssi002-a-2851-from-a-patient-with-juvenile-huntington-disease
#18
Jessica Rosati, Eris Bidollari, Giovannina Rotundo, Daniela Ferrari, Barbara Torres, Laura Bernardini, Federica Consoli, Alessandro De Luca, Iolanda Santimone, Giuseppe Lamorte, Ferdinando Squitieri, Angelo Luigi Vescovi
Huntington Disease (HD) is an autosomal dominant disorder characterized by motor, cognitive and behavioral features caused by a CAG expansion in the HTT gene beyond 35 repeats. The juvenile form (JHD) may begin before the age of 20years and is associated with expanded alleles as long as 60 or more CAG repeats. In this study, induced pluripotent stem cells were generated from skin fibroblasts of a 8-year-old child carrying a large size mutation of 84 CAG repeats in the HTT gene. HD appeared at age 3 with mixed psychiatric (i...
January 9, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29342186/doxorubicin-provoked-increase-of-mitotic-activity-and-concomitant-drain-of-g0-pool-in-therapy-resistant-be-2-c-neuroblastoma
#19
Isabell Hultman, Linnea Haeggblom, Ingvild Rognmo, Josefin Jansson Edqvist, Evelina Blomberg, Rouknuddin Ali, Lottie Phillips, Bengt Sandstedt, Per Kogner, Shahrzad Shirazi Fard, Lars Ährlund-Richter
In this study chemotherapy response in neuroblastoma (NB) was assessed for the first time in a transplantation model comprising non-malignant human embryonic microenvironment of pluripotent stem cell teratoma (PSCT) derived from diploid bona fide hESC. Two NB cell lines with known high-risk phenotypes; the multi-resistant BE(2)-C and the drug sensitive IMR-32, were transplanted to the PSCT model and the tumour growth was exposed to single or repeated treatments with doxorubicin, and thereafter evaluated for cell death, apoptosis, and proliferation...
2018: PloS One
https://www.readbyqxmd.com/read/29342143/regulation-of-embryonic-haematopoietic-multipotency-by-ezh1
#20
Linda T Vo, Melissa A Kinney, Xin Liu, Yuannyu Zhang, Jessica Barragan, Patricia M Sousa, Deepak K Jha, Areum Han, Marcella Cesana, Zhen Shao, Trista E North, Stuart H Orkin, Sergei Doulatov, Jian Xu, George Q Daley
All haematopoietic cell lineages that circulate in the blood of adult mammals derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the blood of mammalian embryos, lineage-restricted progenitors arise first, independently of HSCs, which only emerge later in gestation. As best defined in the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post-coitum. Subsequently, erythroid-myeloid progenitors that express fetal haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and the embryo proper, but these cells lack HSC potential...
January 17, 2018: Nature
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