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Direct Reprogramming

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https://www.readbyqxmd.com/read/28230276/dissection-of-regulatory-elements-during-direct-conversion-of-somatic-cells-into-neurons
#1
Tahereh Soleimani, Nafiseh Falsafi, Hossein Fallahi
A revolutionary approach that involves direct conversion of somatic cells into almost any other types of cells showed promising results for regenerative medicine. Currently, producing valuable cell types including neurons, cardiomyocytes and hepatocytes through direct conversion of somatic cells appear to be a feasible option for regenerative medicine. The process involves inducing the cells by chemical cocktails or by expression of different types of transcription factors. In this concept, in vitro neurogenesis considered to be able to produce neuron cells to replace damaged neurons especially in Alzheimer and Parkinson disease...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28225754/targeting-a-car-to-the-trac-locus-with-crispr-cas9-enhances-tumour-rejection
#2
Justin Eyquem, Jorge Mansilla-Soto, Theodoros Giavridis, Sjoukje J C van der Stegen, Mohamad Hamieh, Kristen M Cunanan, Ashlesha Odak, Mithat Gönen, Michel Sadelain
Chimeric antigen receptors (CARs) are synthetic receptors that redirect and reprogram T cells to mediate tumour rejection. The most successful CARs used to date are those targeting CD19 (ref. 2), which offer the prospect of complete remission in patients with chemorefractory or relapsed B-cell malignancies. CARs are typically transduced into the T cells of a patient using γ-retroviral vectors or other randomly integrating vectors, which may result in clonal expansion, oncogenic transformation, variegated transgene expression and transcriptional silencing...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28223401/transcriptome-analyses-of-rhesus-monkey-pre-implantation-embryos-reveal-a-reduced-capacity-for-dna-double-strand-break-repair-in-primate-oocytes-and-early-embryos
#3
Xinyi Wang, Denghui Liu, Dajian He, Shengbo Suo, Xian Xia, Xiechao He, Jing-Dong Han, Ping Zheng
Pre-implantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA), and cell fate commitment, most of which remain mechanistically unclear in primates. In addition, primates display a high rate of embryo wastage without any clear molecular basis. Understanding the factors involved in genome reprogramming and ZGA will help the generation of induced pluripotent stem cells with high efficiency. Moreover, explaining the molecular basis responsible for embryo wastage in primates will greatly expand our knowledge of species evolution...
February 21, 2017: Genome Research
https://www.readbyqxmd.com/read/28223228/drug-discovery-using-induced-pluripotent-stem-cell-models-of-neurodegenerative-and-ocular-diseases
#4
REVIEW
Sandy S C Hung, Shahnaz Khan, Camden Y Lo, Alex W Hewitt, Raymond C B Wong
The revolution of induced pluripotent stem cell (iPSC) technology provides a platform for development of cell therapy, disease modeling and drug discovery. Recent technological advances now allow us to reprogram a patient's somatic cells into induced pluripotent stem cells (iPSCs). Together with methods to differentiate these iPSCs into the disease-relevant cell types, we are now able to model disease in vitro using iPSCs. Importantly, this represents a robust in vitro platform using patient-specific cells, providing opportunity for personalized precision medicine...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28221248/early-transcriptomic-changes-in-the-ileal-pouch-provide-insight-into-the-molecular-pathogenesis-of-pouchitis-and-ulcerative-colitis
#5
Yong Huang, Sushila Dalal, Dionysios Antonopoulos, Nathaniel Hubert, Laura H Raffals, Kyle Dolan, Christopher Weber, Jeannette S Messer, Bana Jabri, Albert Bendelac, A Murat Eren, David T Rubin, Mitch Sogin, Eugene B Chang
BACKGROUND: Ulcerative colitis (UC) only involves the colonic mucosa. Yet, nearly 50% of patients with UC who undergo total proctocolectomy with ileal pouch anal anastomosis develop UC-like inflammation of the ileal pouch (pouchitis). By contrast, patients with familial adenomatous polyposis (FAP) with ileal pouch anal anastomosis develop pouchitis far less frequently. We hypothesized that pathogenic events associated with the development of UC are recapitulated by colonic-metaplastic transcriptomic reprogramming of the UC pouch...
March 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28216149/direct-generation-of-human-neuronal-cells-from-adult-astrocytes-by-small-molecules
#6
Longfei Gao, Wuqiang Guan, Min Wang, Huihan Wang, Jiali Yu, Qing Liu, Binlong Qiu, Yongchun Yu, Yifang Ping, Xiuwu Bian, Li Shen, Gang Pei
Astrocytes, due to the proximity to neuronal lineage and capability to proliferate, are ideal starting cells to regenerate neurons. Human fetal astrocytes have been successfully converted into neuronal cells by small molecules, which offered a broader range of further applications than transcription factor-mediated neuronal reprogramming. Here we report that human adult astrocytes could also be converted into neuronal cells by a different set of small molecules. These induced cells exhibited typical neuronal morphologies, expressed neuronal markers, and displayed neuronal electrophysiological properties...
February 7, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28215747/unexpected-acoustic-stimulation-during-action-preparation-reveals-gradual-re-specification-of-movement-direction
#7
Welber Marinovic, James Tresilian, Jack L Chapple, Stephan Riek, Timothy Carroll
A loud acoustic stimulus (LAS) is often used as a tool to investigate motor preparation in simple reaction time (RT) tasks, where all movement parameters are known in advance. In this report, we used a LAS to examinedirection specification in simple and choice RT tasks. This allowed us toinvestigatehow the specification of movement direction unfolds during the preparation period. In two experiments, participants responded to the appearance of an imperative stimulus (IS) with a ballistic wrist force directed towards one of two targets...
February 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28210262/morphoproteomic-guided-host-directed-therapy-for-tuberculosis
#8
Robert E Brown, Robert L Hunter, Shen-An Hwang
In an effort to develop more effective therapy for tuberculosis (TB), research efforts are looking toward host-directed therapy, reprograming the body's natural defenses to better control the infection. While significant progress is being made, the efforts are limited by lack of understanding of the pathology and pathogenesis of adult type TB disease. We have recently published evidence that the developing lesions in human lungs are focal endogenous lipid pneumonia that constitutes a region of local susceptibility in a person with strong systemic immunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28209718/demethylation-of-h3k27-is-essential-for-the-induction-of-direct-cardiac-reprogramming-by-mir-combo
#9
Sophie Dal-Pra, Conrad P Hodgkinson, Maria Mirotsou, Imke Kirste, Victor J Dzau
Rationale: Direct reprogramming of cardiac fibroblasts to cardac omyocytes has recently emerged as a novel and promising approach to regenerate the injured myocardium. We have previously demonstrated the feasibility of this approach in vitro and in vivo using a combination of four microRNAs (miR-1, miR-133, miR-208 and miR-499) that we named miR combo. However, the mechanism of miR combo mediated direct cardiac reprogramming is currently unknown. Objective: Here we investigated the possibility that miR combo initiated direct cardiac reprogramming through an epigenetic mechanism...
February 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28209385/a-comparison-of-the-pro-angiogenic-potential-of-human-induced-pluripotent-stem-cell-derived-endothelial-cells-and-induced-endothelial-cells-in-a-murine-model-of-peripheral-arterial-disease
#10
Zoe E Clayton, Gloria S C Yuen, Sara Sadeghipour, Jack D Hywood, Jack W T Wong, Ngan F Huang, Martin K C Ng, John P Cooke, Sanjay Patel
BACKGROUND: Endothelial cells derived from human induced pluripotent stem cells (iPSC-ECs) promote angiogenesis, and more recently induced endothelial cells (iECs) have been generated via fibroblast trans-differentiation. These cell types have potential as treatments for peripheral arterial disease (PAD). However, it is unknown whether different reprogramming methods produce cells that are equivalent in terms of their pro-angiogenic capabilities. OBJECTIVES: We aimed to directly compare iPSC-ECs and iECs in an animal model of PAD, in order to identify which cell type, if any, displays superior therapeutic potential...
January 31, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28199843/the-sin3a-hdac-corepressor-complex-functionally-cooperates-with-nanog-to-promote-pluripotency
#11
Arven Saunders, Xin Huang, Miguel Fidalgo, Michael H Reimer, Francesco Faiola, Junjun Ding, Carlos Sánchez-Priego, Diana Guallar, Carmen Sáenz, Dan Li, Jianlong Wang
Although SIN3A is required for the survival of early embryos and embryonic stem cells (ESCs), the role of SIN3A in the maintenance and establishment of pluripotency remains unclear. Here, we find that the SIN3A/HDAC corepressor complex maintains ESC pluripotency and promotes the generation of induced pluripotent stem cells (iPSCs). Members of the SIN3A/HDAC corepressor complex are enriched in an extended NANOG interactome and function in transcriptional coactivation in ESCs. We also identified a critical role for SIN3A and HDAC2 in efficient reprogramming of somatic cells...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28197667/discovery-and-progress-of-direct-cardiac-reprogramming
#12
REVIEW
Hidenori Kojima, Masaki Ieda
Cardiac disease remains a major cause of death worldwide. Direct cardiac reprogramming has emerged as a promising approach for cardiac regenerative therapy. After the discovery of MyoD, a master regulator for skeletal muscle, other single cardiac reprogramming factors (master regulators) have been sought. Discovery of cardiac reprogramming factors was inspired by the finding that multiple, but not single, transcription factors were needed to generate induced pluripotent stem cells (iPSCs) from fibroblasts. We first reported a combination of cardiac-specific transcription factors, Gata4, Mef2c, and Tbx5 (GMT), that could convert mouse fibroblasts into cardiomyocyte-like cells, which were designated as induced cardiomyocyte-like cells (iCMs)...
February 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28193136/ccctc-binding-factor-ctcf-transcriptionally-targets-wdr5-to-mediate-somatic-cell-reprogramming
#13
Feng Wang, Jinghua Han, Li Wang, Ying Jing, Zhu Zhu, Dawei Hui, Zhaohui Wang, Yangzi Wang, Yang Dong, Tao Tan
It was previously reported that WD repeat domain 5 (Wdr5), a core member of the mammalian Trithorax complex, is a key regulator for the maintenance of ES cell pluripotency and somatic cell reprogramming. However, it remains unclear whether other factors also involve in this process. Here, we show that CTCF is an upstream regulator of Wdr5, it physically associates with Wdr5 and further transcriptionally controls its expression by directly targeting on Wdr5 gene promoter. As a downstream effector, overexpression of Wdr5 can rescue ES cells growth defect and decreased formation of induced pluripotent stem (iPS) cells caused by CTCF knockdown...
February 14, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28191784/derivation-of-transgene-free-rat-induced-pluripotent-stem-cells-approximating-the-quality-of-embryonic-stem-cells
#14
Shuping Li, He Lan, Hongsheng Men, Yuanyuan Wu, Ning Li, Mario R Capecchi, Elizabeth C Bryda, Sen Wu
Although a variety of reprogramming strategies have been reported to create transgene-free induced pluripotent stem (iPS) cells from differentiated cell sources, a fundamental question still remains: Can we generate safe iPS cells that have the full spectrum of features of corresponding embryonic stem (ES) cells? Studies in transgene-free mouse iPS cells have indicated a positive answer to this question. However, the reality is that no other species have a derived transgene-free iPS cell line that can truly mimic ES cell quality...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28191764/neural-progenitor-like-cells-induced-from-human-gingiva-derived-mesenchymal-stem-cells-regulate-myelination-of-schwann-cells-in-rat-sciatic-nerve-regeneration
#15
Qunzhou Zhang, Phuong Nguyen, Qilin Xu, Wonse Park, Sumin Lee, Akihiro Furuhashi, Anh D Le
Regeneration of peripheral nerve injury remains a major clinical challenge. Recently, mesenchymal stem cells (MSCs) have been considered as potential candidates for peripheral nerve regeneration; however, the underlying mechanisms remain elusive. Here, we show that human gingiva-derived MSCs (GMSCs) could be directly induced into multipotent NPCs (iNPCs) under minimally manipulated conditions without the introduction of exogenous genes. Using a crush-injury model of rat sciatic nerve, we demonstrate that GMSCs transplanted to the injury site could differentiate into neuronal cells, whereas iNPCs could differentiate into both neuronal and Schwann cells...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28186702/direct-conversion-of-human-fibroblasts-into-schwann-cells-that-facilitate-regeneration-of-injured-peripheral-nerve-in-vivo
#16
Yoshihiro Sowa, Tsunao Kishida, Koichi Tomita, Kenta Yamamoto, Toshiaki Numajiri, Osam Mazda
Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs)...
January 9, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28184935/involvement-of-ezh2-in-aerobic-glycolysis-of-prostate-cancer-through-mir-181b-hk2-axis
#17
Tao Tao, Ming Chen, Ranran Jiang, Han Guan, Yeqing Huang, Huan Su, Qiang Hu, Xu Han, Jun Xiao
Recent studies suggest that several types of tumors preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. However, it remains largely unexplored whether metabolic reprogramming is involved in prostate cancer (PCa) progression. In this study, we found that histone methyltransferase enhancer of zeste homolog 2 (EZH2) dysregulated in PCa development regulated cellular growth and aerobic glycolysis through miR-181b/hexokinase 2 (HK2) axis. Aberrant expression profiles of coding RNA and microRNA were examined by two large, independent clinical prostate cancer data sets...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28169300/two-factor-based-reprogramming-of-rodent-and-human-fibroblasts-into-schwann-cells
#18
Pietro Giuseppe Mazzara, Luca Massimino, Marta Pellegatta, Giulia Ronchi, Alessandra Ricca, Angelo Iannielli, Serena Gea Giannelli, Marco Cursi, Cinzia Cancellieri, Alessandro Sessa, Ubaldo Del Carro, Angelo Quattrini, Stefano Geuna, Angela Gritti, Carla Taveggia, Vania Broccoli
Schwann cells (SCs) generate the myelin wrapping of peripheral nerve axons and are promising candidates for cell therapy. However, to date a renewable source of SCs is lacking. In this study, we show the conversion of skin fibroblasts into induced Schwann cells (iSCs) by driving the expression of two transcription factors, Sox10 and Egr2. iSCs resembled primary SCs in global gene expression profiling and PNS identity. In vitro, iSCs wrapped axons generating compact myelin sheaths with regular nodal structures...
February 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28166968/interspecies-somatic-cell-nuclear-transfer-in-asiatic-cheetah-using-nuclei-derived-from-post-mortem-frozen-tissue-in-absence-of-cryo-protectant-and-in%C3%A2-vitro-matured-domestic-cat-oocytes
#19
F Moulavi, S M Hosseini, N Tanhaie-Vash, S Ostadhosseini, S H Hosseini, M Hajinasrollah, M H Asghari, H Gourabi, A Shahverdi, A D Vosough, M H Nasr-Esfahani
Recent accomplishments in the field of somatic cell nuclear transfer (SCNT) hold tremendous promise to prevent rapid loss of animal genetic resources using ex situ conservation technology. Most of SCNT studies use viable cells for nuclear transfer into recipient oocytes. However, preparation of live cells in extreme circumstances, in which post-mortem material of endangered/rare animals is improperly retained frozen, is difficult, if not impossible. This study investigated the possibility of interspecies-SCNT (iSCNT) in Asiatic cheetah (Acinonyx jubatus venaticus), a critically endangered subspecies, using nuclei derived from frozen tissue in absence of cryo-protectant at -20 °C and in vitro matured domestic cat oocytes...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28145631/generation-of-integration-free-induced-neurons-using-graphene-oxide-polyethylenimine
#20
Soonbong Baek, Jaesur Oh, Juhyun Song, Hwan Choi, Junsang Yoo, Gui-Yeon Park, Jin Han, Yujung Chang, Hanseul Park, Hongwon Kim, Ssang-Goo Cho, Byung-Soo Kim, Jongpil Kim
Direct conversion of somatic cells into induced neurons (iNs) without inducing pluripotency has great therapeutic potential for treating central nervous system diseases. Reprogramming of somatic cells to iNs requires the introduction of several factors that drive cell-fate conversion, and viruses are commonly used to deliver these factors into somatic cells. However, novel gene-delivery systems that do not integrate transgenes into the genome are required to generate iNs for safe human clinical applications...
February 2017: Small
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