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Direct Reprogramming

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https://www.readbyqxmd.com/read/29777905/coupling-of-the-polyamine-and-iron-metabolism-pathways-in-the-regulation-of-proliferation-mechanistic-links-to-alterations-in-key-polyamine-biosynthetic-and-catabolic-enzymes
#1
Darius J R Lane, Dong-Hun Bae, Aritee R Siafakas, Yohan Suryo Rahmanto, Lina Al-Akra, Patric J Jansson, Robert A Casero, Des R Richardson
Many biological processes result from the coupling of metabolic pathways. Considering this, proliferation depends on adequate iron and polyamines, and although iron-depletion impairs proliferation, the metabolic link between iron and polyamine metabolism has never been thoroughly investigated. This is important to decipher, as many disease states demonstrate co-dysregulation of iron and polyamine metabolism. Herein, for the first time, we demonstrate that cellular iron levels robustly regulate 13 polyamine pathway proteins...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29769670/new-approaches-for-brain-repair-from-rescue-to-reprogramming
#2
REVIEW
Roger A Barker, Magdalena Götz, Malin Parmar
The ability to repair or promote regeneration within the adult human brain has been envisioned for decades. Until recently, such efforts mainly involved delivery of growth factors and cell transplants designed to rescue or replace a specific population of neurons, and the results have largely been disappointing. New approaches using stem-cell-derived cell products and direct cell reprogramming have opened up the possibility of reconstructing neural circuits and achieving better repair. In this Review we briefly summarize the history of neural repair and then discuss these new therapeutic approaches, especially with respect to chronic neurodegenerative disorders...
May 2018: Nature
https://www.readbyqxmd.com/read/29763372/acetyl-coa-from-inflammation-induced-fatty-acids-oxidation-promotes-hepatic-malate-aspartate-shuttle-activity-and-glycolysis
#3
Tongxin Wang, Weilei Yao, Ji Li, Qiongyu He, Yafei Shao, Feiruo Huang
Hepatic metabolic syndrome is associated with inflammation, as it stimulates the reprogramming of nutrient metabolism and hepatic mitochondria-generated acetyl-CoA. But how acetyl-CoA affects the reprogramming of nutrient metabolism, especially glucose and fatty acids, in the condition of inflammation is still unclear. Here, we used an acute inflammation model in which pigs were injected with lipopolysaccharide (LPS), and found that hepatic glycolysis and fatty acid oxidation are both promoted. Acetyl-proteome profiling of LPS-infected pigs liver showed that inflammatory stress exacerbates the acetylation of mitochondrial proteins...
May 15, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29760724/adult-neural-stem-cells-basic-research-and-production-strategies-for-neurorestorative-therapy
#4
REVIEW
E M Samoilova, V A Kalsin, N M Kushnir, D A Chistyakov, A V Troitskiy, V P Baklaushev
Over many decades, constructing genetically and phenotypically stable lines of neural stem cells (NSC) for clinical purposes with the aim of restoring irreversibly lost functions of nervous tissue has been one of the major goals for multiple research groups. The unique ability of stem cells to maintain their own pluripotent state even in the adult body has made them into the choice object of study. With the development of the technology for induced pluripotent stem cells (iPSCs) and direct transdifferentiation of somatic cells into the desired cell type, the initial research approaches based on the use of allogeneic NSCs from embryonic or fetal nervous tissue are gradually becoming a thing of the past...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29760595/application-of-induced-pluripotency-in-cancer-studies
#5
REVIEW
Patrycja Czerwińska, Sylwia Mazurek, Maciej Wiznerowicz
As soon as induced pluripotent stem cells (iPSCs) reprogramming of somatic cells were developed, the discovery attracted the attention of scientists, offering new perspectives for personalized medicine and providing a powerful platform for drug testing. The technology was almost immediately applied to cancer studies. As presented in this review, direct reprogramming of cancer cells with enforced expression of pluripotency factors have several basic purposes, all of which aim to explain the complex nature of cancer development and progression, therapy-resistance and relapse, and ultimately lead to the development of novel anti-cancer therapies...
May 2018: Reports of Practical Oncology and Radiotherapy
https://www.readbyqxmd.com/read/29754960/high-level-precise-knockin-of-ipscs-by-simultaneous-reprogramming-and-genome-editing-of-human-peripheral-blood-mononuclear-cells
#6
Wei Wen, Xinxin Cheng, Yawen Fu, Feiying Meng, Jian-Ping Zhang, Lu Zhang, Xiao-Lan Li, Zhixue Yang, Jing Xu, Feng Zhang, Gary D Botimer, Weiping Yuan, Changkai Sun, Tao Cheng, Xiao-Bing Zhang
We have developed an improved episomal vector system for efficient generation of integration-free induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells. More recently, we reported that the use of an optimized CRISPR-Cas9 system together with a double-cut donor increases homology-directed repair-mediated precise gene knockin efficiency by 5- to 10-fold. Here, we report the integration of blood cell reprogramming and genome editing in a single step. We found that expression of Cas9 and KLF4 using a single vector significantly increases genome editing efficiency, and addition of SV40LT further enhances knockin efficiency...
May 4, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29748591/mir-3662-suppresses-hepatocellular-carcinoma-growth-through-inhibition-of-hif-1%C3%AE-mediated-warburg-effect
#7
Zhiqiang Chen, Xueliang Zuo, Yao Zhang, Guoyong Han, Long Zhang, Jindao Wu, Xuehao Wang
Glucose metabolic reprogramming from oxidative to aerobic glycolysis, referred as the Warburg effect, is a hallmark of tumor cells. Accumulating evidence suggests that a subset of microRNAs play pivotal roles in modulating such reprogramming of glucose metabolism in cancer cells. miR-3662 has been implicated previously in both pro-tumorigenic and anti-tumorigenic effects in several types of cancer. The expression level of miR-3662 is downregulated in acute myeloid leukemia, whereas increased miR-3662 expression is observed in lung adenocarcinoma...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29746091/a-framework-for-engineering-stress-resilient-plants-using-genetic-feedback-control-and-regulatory-network-rewiring
#8
Mathias Foo, Iulia Gherman, Peijun Zhang, Declan G Bates, Katherine Denby
Crop disease leads to significant waste world-wide, both pre- and post-harvest, with subsequent economic and sustainability consequences. Disease outcome is determined both by the plants' response to the pathogen and by the ability of the pathogen to suppress defense responses and manipulate the plant to enhance colonization. The defense response of a plant is characterized by significant transcriptional reprogramming mediated by underlying gene regulatory networks and components of these networks are often targeted by attacking pathogens...
May 10, 2018: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29743891/a-loss-of-function-screen-of-epigenetic-modifiers-and-splicing-factors-during-early-stage-of-cardiac-reprogramming
#9
Yang Zhou, Sahar Alimohamadi, Li Wang, Ziqing Liu, Joseph B Wall, Chaoying Yin, Jiandong Liu, Li Qian
Direct reprogramming of cardiac fibroblasts (CFs) to induced cardiomyocytes (iCMs) is a newly emerged promising approach for cardiac regeneration, disease modeling, and drug discovery. However, its potential has been drastically limited due to the low reprogramming efficiency and largely unknown underlying molecular mechanisms. We have previously screened and identified epigenetic factors related to histone modification during iCM reprogramming. Here, we used shRNAs targeting an additional battery of epigenetic factors involved in chromatin remodeling and RNA splicing factors to further identify inhibitors and facilitators of direct cardiac reprogramming...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29743499/reprogramming-oscillations-and-transdifferentiation-in-epigenetic-landscapes
#10
Bivash Kaity, Ratan Sarkar, Buddhapriya Chakrabarti, Mithun K Mitra
Waddington's epigenetic landscape provides a phenomenological understanding of the cell differentiation pathways from the pluripotent to mature lineage-committed cell lines. In light of recent successes in the reverse programming process there has been significant interest in quantifying the underlying landscape picture through the mathematics of gene regulatory networks. We investigate the role of time delays arising from multi-step chemical reactions and epigenetic rearrangement on the cell differentiation landscape for a realistic two-gene regulatory network, consisting of self-promoting and mutually inhibiting genes...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29742392/direct-reprogramming-of-mouse-fibroblasts-into-functional-skeletal-muscle-progenitors
#11
Ori Bar-Nur, Mattia F M Gerli, Bruno Di Stefano, Albert E Almada, Amy Galvin, Amy Coffey, Aaron J Huebner, Peter Feige, Cassandra Verheul, Priscilla Cheung, Duygu Payzin-Dogru, Sylvain Paisant, Anthony Anselmo, Ruslan I Sadreyev, Harald C Ott, Shahragim Tajbakhsh, Michael A Rudnicki, Amy J Wagers, Konrad Hochedlinger
Skeletal muscle harbors quiescent stem cells termed satellite cells and proliferative progenitors termed myoblasts, which play pivotal roles during muscle regeneration. However, current technology does not allow permanent capture of these cell populations in vitro. Here, we show that ectopic expression of the myogenic transcription factor MyoD, combined with exposure to small molecules, reprograms mouse fibroblasts into expandable induced myogenic progenitor cells (iMPCs). iMPCs express key skeletal muscle stem and progenitor cell markers including Pax7 and Myf5 and give rise to dystrophin-expressing myofibers upon transplantation in vivo...
May 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29739872/chemical-compound-based-direct-reprogramming-for-future-clinical-applications
#12
REVIEW
Yukimasa Takeda, Yoshinori Harada, Toshikazu Yoshikawa, Ping Dai
Recent studies have revealed that a combination of chemical compounds enables direct reprogramming from one somatic cell type into another without the use of transgenes by regulating cellular signaling pathways and epigenetic modifications. The generation of induced pluripotent stem (iPS) cells generally requires virus vector-mediated expression of multiple transcription factors, which might disrupt genomic integrity and proper cell functions. The direct reprogramming is a promising alternative to rapidly prepare different cell types by bypassing the pluripotent state...
June 29, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29739823/butyrate-suppresses-the-proliferation-of-colorectal-cancer-cells-via-targeting-pyruvate-kinase-m2-and-metabolic-reprogramming
#13
Qingran Li, Lijuan Cao, Yang Tian, Pei Zhang, Chujie Ding, Wenjie Lu, Chenxi Jia, Chang Shao, Wenyue Liu, Dong Wang, Hui Ye, Haiping Hao
Butyrate is a short chain fatty acid present in a high concentration in the gut lumen. It has been well documented that butyrate, by serving as an energetic metabolite, promotes the proliferation of normal colonocytes while, by serving as a histone deacetylase inhibitor, epigenetically suppressing the proliferation of cancerous counterparts undergoing the Warburg effect. However, how butyrate interrupts the metabolism of colorectal cancer cells and ultimately leads to the suppression of cell proliferation remains unclear...
May 8, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29735761/metabolic-reprogramming-of-vibrio-cholerae-impaired-in-respiratory-nadh-oxidation-is-accompanied-with-increased-copper-sensitivity
#14
Charlotte Toulouse, Kristina Metesch, Jens Pfannstiel, Julia Steuber
The electrogenic, sodium ion translocating NADH:quinone oxidoreductase (NQR) from Vibrio cholerae is frequent in pathogenic bacteria and a potential target for antibiotics. NQR couples the oxidation of NADH to the formation of a sodium motive force (SMF) and therefore drives important processes such as flagellar rotation, substrate uptake, and energy-dissipating cation-proton antiport. We performed a quantitative proteome analysis of V. cholerae O395N1 in comparison to its variant lacking the NQR using minimal medium with glucose as carbon source...
May 7, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29734659/s-phase-synchronization-facilitates-the-early-progression-of-induced-cardiomyocyte-reprogramming-through-enhanced-cell-cycle-exit
#15
Emre Bektik, Adrienne Dennis, Gary Pawlowski, Chen Zhou, Danielle Maleski, Satoru Takahashi, Kenneth R Laurita, Isabelle Deschênes, Ji-Dong Fu
Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming...
May 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29732051/dual-targeting-biomimetic-delivery-for-anti-glioma-activity-via-remodeling-the-tumor-microenvironment-and-directing-macrophage-mediated-immunotherapy
#16
Pengfei Zhao, Yonghui Wang, Xuejia Kang, Aihua Wu, Weimin Yin, Yisi Tang, Jinyu Wang, Meng Zhang, Yifei Duan, Yongzhuo Huang
Tumor-associated macrophages (TAMs) are the major components in the tumor microenvironment (TME). The polarization from the protumor M2 (TAM2) to antitumor M1 (TAM1) phenotype can not only lift the immunosuppressive constraints and elicit cytotoxic T-cell immunity but also augment the chemotherapy efficacy. However, the treatment feasibility by TAM modulation in brain tumors and the mechanisms remained unknown. A dual-targeting biomimetic codelivery and treatment strategy was developed for anti-glioma activity...
March 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29731772/direct-cardiac-reprogramming-progress-and-promise
#17
REVIEW
James L Engel, Reza Ardehali
The human adult heart lacks a robust endogenous repair mechanism to fully restore cardiac function after insult; thus, the ability to regenerate and repair the injured myocardium remains a top priority in treating heart failure. The ability to efficiently generate a large number of functioning cardiomyocytes capable of functional integration within the injured heart has been difficult. However, the ability to directly convert fibroblasts into cardiomyocyte-like cells both in vitro and in vivo offers great promise in overcoming this problem...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29731494/variation-in-the-phenotype-of-photosensitive-cells-produced-from-human-fibroblast-cell-lines
#18
Toshiyuki Ishii, Chengzhu Yin, Yuko Seko, Akihiro Umezawa, Makoto Kaneda
BACKGROUND: Photoreceptors differentiated from somatic cells are a useful tool for transplantation and drug screening. We previously showed that photosensitive cells are differentiated from human fibroblasts by direct reprogramming. In induced pluripotent stem (iPS) cells or embryonic stem (ES) cells, the properties of differentiated cells differ among the source of cell lines. However, whether or not the properties of the photosensitive cells produced by direct reprogramming are controlled by the origin of the cell line remains unknown...
2018: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/29728053/changes-in-nitrogen-availability-lead-to-a-reprogramming-of-pyruvate-metabolism
#19
Nazeer Fataftah, Christina Mohr, Mohammad-Reza Hajirezaei, Nicolaus von Wirén, Klaus Humbeck
BACKGROUND: Low availability of nitrogen (N) severely affects plant growth at different levels, which can be reverted by the resupply of N. To unravel the critical steps in primary metabolism underlying the growth adjustment in response to changes in N availability, transcriptomic and comprehensive metabolite analyses were performed in barley using primary leaves at early and later stages of N deprivation, and after N resupply to N-deficient plants. RESULT: N deficiency in leaves caused differential regulation of 1947 genes, mostly belonging to the functional classes photosynthesis, cell wall degradation, lipid degradation, amino acid degradation, transcription factors, phytohormone metabolism and receptor-like kinases...
May 4, 2018: BMC Plant Biology
https://www.readbyqxmd.com/read/29726937/design-principles-for-nuclease-deficient-crispr-based-transcriptional-regulators
#20
Michael K Jensen
The engineering of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated proteins continues to expand the toolkit available for genome editing, reprogramming gene regulation, genome visualisation and epigenetic studies of living organisms. In this review, the emerging design principles on the use of nuclease-deficient CRISPR-based reprogramming of gene expression will be presented. The review will focus on the designs implemented in yeast both at the level of CRISPR proteins and guide RNA (gRNA), but will lend due credits to the seminal studies performed in other species where relevant...
June 1, 2018: FEMS Yeast Research
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