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https://www.readbyqxmd.com/read/29222327/mitochondrially-produced-atp-affects-stem-cell-pluripotency-via-actl6a-mediated-histone-acetylation
#1
Ying Zhang, Peng Cui, Yuhuan Li, Guihai Feng, Man Tong, Lu Guo, Tianda Li, Lei Liu, Wei Li, Qi Zhou
ATP is mainly generated by glycolysis in pluripotent stem cells (PSCs) and is consumed to maintain cell viability. Differences in mitochondrial activity among induced (i)PSCs with different degrees of pluripotency are poorly understood. In this study, by comparing gene expression and mitochondrial activity among iPSCs with different degrees of pluripotency, we found that mitochondrial complex I gene expression, complex I activity, and cellular ATP levels were much higher in fully pluripotent stem cell lines than in partially pluripotent stem cell lines...
December 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29220667/transient-and-permanent-reconfiguration-of-chromatin-and-transcription-factor-occupancy-drive-reprogramming
#2
Anja S Knaupp, Sam Buckberry, Jahnvi Pflueger, Sue Mei Lim, Ethan Ford, Michael R Larcombe, Fernando J Rossello, Alex de Mendoza, Sara Alaei, Jaber Firas, Melissa L Holmes, Shalima S Nair, Susan J Clark, Christian M Nefzger, Ryan Lister, Jose M Polo
Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) induces changes in genome architecture reflective of the embryonic stem cell (ESC) state. However, only a small minority of cells typically transition to pluripotency, which has limited our understanding of the process. Here, we characterize the DNA regulatory landscape during reprogramming by time-course profiling of isolated sub-populations of intermediates poised to become iPSCs. Widespread reconfiguration of chromatin states and transcription factor (TF) occupancy occurs early during reprogramming, and cells that fail to reprogram partially retain their original chromatin states...
December 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29220666/chromatin-accessibility-dynamics-during-ipsc-reprogramming
#3
Dongwei Li, Jing Liu, Xuejie Yang, Chunhua Zhou, Jing Guo, Chuman Wu, Yue Qin, Lin Guo, Jiangping He, Shenyong Yu, He Liu, Xiaoshan Wang, Fang Wu, Junqi Kuang, Andrew P Hutchins, Jiekai Chen, Duanqing Pei
Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics...
December 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29220662/ipsc-reprogramming-is-not-just-an-open-and-shut-case
#4
Peter C Scacheri, Paul J Tesar
What exactly happens to chromatin as cells undergo an identity change? In this issue of Cell Stem Cell, Li et al. (2017) and Knaupp et al. (2017) offer new insights by mapping in exquisite detail chromatin accessibility dynamics as mouse embryonic fibroblasts are reprogrammed into induced pluripotent stem cells.
December 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29217433/hypertrophic-cardiomyopathy-linked-mutation-in-troponin-t-causes-myofibrillar-disarray-and-pro-arrhythmic-action-potential-changes-in-human-ipsc-cardiomyocytes
#5
Lili Wang, Kyungsoo Kim, Shan Parikh, Adrian Gabriel Cadar, Kevin R Bersell, Huan He, Jose R Pinto, Dmytro O Kryshtal, Bjorn C Knollmann
BACKGROUND: Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. OBJECTIVES: To study the effects of the TnT-I79N mutation in human cardiomyocytes...
December 4, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29217199/efficient-generation-of-transgene-and-feeder-free-induced-pluripotent-stem-cells-from-human-dental-mesenchymal-stem-cells-and-their-chemically-defined-differentiation-into-cardiomyocytes
#6
Xiaobing Tan, Qingli Dai, Tao Guo, Jingshu Xu, Qingyuan Dai
Advance in stem cell research resulted in several processes to generate induced pluripotent stem cells (iPSCs) from adult somatic cells. In our previous study, the reprogramming of iPSCs from human dental mesenchymal stem cells (MSCs) including SCAP and DPSCs, has been reported. Herein, safe iPSCs were reprogrammed from SCAP and DPSCs using non-integrating RNA virus vector, which is an RNA virus carrying no risk of altering host genome. DPSCs- and SCAP-derived iPSCs exhibited the characteristics of the classical morphology with human embryonic stem cells (hESCs) without integration of foreign genes, indicating the potential of their clinical application...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29216777/the-long-and-winding-road-stem-cells-for-cystic-fibrosis
#7
Massimo Conese, Elisa Beccia, Stefano Castellani, Sante Di Gioia, Carla Colombo, Antonella Angiolillo, Annalucia Carbone
Cystic fibrosis (CF) is a genetic syndrome with a high mortality rate due to severe lung disease. Despite having several drugs targeting specific mutated CFTR proteins already in clinical trials, new therapies, based on stem cells, are also emerging to treat those patients. Areas covered: The authors review the main sources of stem cells, including embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs), gestational stem cells, and adult stem cells, such as mesenchymal stem cells (MSCs) in the context of CF...
December 8, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29215942/cocktail-of-chemical-compounds-and-recombinant-proteins-robustly-promote-the-stemness-of-adipose-derived-stem-cells
#8
Yonglong Guo, Quan Yu, Sanjana Mathew, Ruiling Lian, Yunxia Xue, Zekai Cui, Shanyi Li, Deliang Zhu, Yuting Han, Qiaolang Zeng, Shiwei Liu, Jiansu Chen
Induced pluripotent stem cells (iPSCs) from somatic cells can be reprogrammed to provide an unlimited cell resource showing great potential in disease modeling and regenerative medicine. However, the traditional method for reprogramming cells into iPSCs using genome-integrating retro- or lenti-viruses remain an obstacle for its application in clinical settings. We tried the possibility to generate pre-iPSCs from human adipose-derived stem cells (ADSCs) by nongenetic reprogramming using recombinant cell-penetrating proteins OCT4/KLF4/SOX2 (PTD-OKS) and the cocktail of small molecules (VCFZ)...
December 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/29214501/mouse-embryonic-fibroblast-mef-bmp4-conditioned-medium-enhanced-multipotency-of-human-dental-pulp-cells
#9
Lu Liu, Zhengjun Peng, Zhezhen Xu, Haoquan Huang, Xi Wei
Dental pulp cells (DPCs) are valuable cell source for dental regeneration, albeit their application is restricted by limited pluripotency due to current culture condition. Mouse embryonic fibroblasts (MEFs) are served as feeder layer to maintain undifferentiated state of iPSCs and ESCs with long-term in vitro culture. Bone morphogenetic protein 4 (BMP4) plays an important role in the regulation of undifferentiated state and lineage commitment of cells through modulation of microenvironment. However, so far little was known how micro environment affect the multipotency of dental derived cells...
December 6, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29212799/lif-activated-jak-signaling-determines-esrrb-expression-during-late-stage-reprogramming
#10
Delun Huang, Ling Wang, Jingyue Duan, Chang Huang, Xiuchun Cindy Tian, Ming Zhang, Young Tang
The regulatory process of naïve-state induced pluripotent stem cells (iPSCs) generation is not well understood. Leukemia inhibitory factor (LIF) activated Janus kinase/signal transducer and activator of transcription 3 (Jak/Stat3) is the master regulator for naïve-state pluripotency achievement and maintenance. The estrogen-related receptor beta (Esrrb) serves as a naïve-state marker gene regulating self-renewal of embryonic stem cells (ESCs). However, the inter-connection between Esrrb and LIF signaling for pluripotency establishment in reprogramming is unclear...
December 6, 2017: Biology Open
https://www.readbyqxmd.com/read/29212711/ppar%C3%AE-activation-by-bexarotene-promotes-neuroprotection-by-restoring-bioenergetic-and-quality-control-homeostasis
#11
Audrey S Dickey, Dafne N Sanchez, Martin Arreola, Kunal R Sampat, Weiwei Fan, Nicolas Arbez, Sergey Akimov, Michael J Van Kanegan, Kohta Ohnishi, Stephen K Gilmore-Hall, April L Flores, Janice M Nguyen, Nicole Lomas, Cynthia L Hsu, Donald C Lo, Christopher A Ross, Eliezer Masliah, Ronald M Evans, Albert R La Spada
Neurons must maintain protein and mitochondrial quality control for optimal function, an energetically expensive process. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that promote mitochondrial biogenesis and oxidative metabolism. We recently determined that transcriptional dysregulation of PPARδ contributes to Huntington's disease (HD), a progressive neurodegenerative disorder resulting from a CAG-polyglutamine repeat expansion in the huntingtin gene. We documented that the PPARδ agonist KD3010 is an effective therapy for HD in a mouse model...
December 6, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29212199/klf4-reduces-stemness-phenotype-triggers-mesenchymal-epithelial-transition-met-like-molecular-changes-and-prevents-tumor-progression-in-nasopharygeal-carcinoma
#12
Xiqing Li, Zhunlan Zhao, Xiaoling Zhang, Sheng Yang, Xia Lin, Xinglong Yang, Xiaolin Lin, Junwen Shi, Shengchun Wang, Wentao Zhao, Jing Li, Fei Gao, Mingyue Liu, Ning Ma, Weiren Luo, Kaitai Yao, Yan Sun, Shengjun Xiao, Dong Xiao, Junshuang Jia
The reprogramming factor Krüppel-like factor 4 (Klf4), one of the Yamanaka's reprogramming factors, plays an essential role in reprogramming somatic cells into induced pluripotent stem cells (iPSCs). Klf4 is dysregulated and displays divergent functions in multiple malignancies, but the biological roles of Klf4 in nasopharyngeal carcinoma (NPC) remain unknown. The present study revealed that Klf4 downregulation in a cohort of human NPC biopsies is significantly associated with invasive and metastatic phenotypes of NPC...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212016/cellular-phenotypes-in-human-ipsc-derived-neurons-from-a-genetic-model-of-autism-spectrum-disorder
#13
Aditi Deshpande, Smita Yadav, Dang Q Dao, Zhi-Yong Wu, Kenton C Hokanson, Michelle K Cahill, Arun P Wiita, Yuh-Nung Jan, Erik M Ullian, Lauren A Weiss
A deletion or duplication in the 16p11.2 region is associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. In addition to clinical characteristics, carriers of the 16p11.2 copy-number variant (CNV) manifest opposing neuroanatomical phenotypes-e.g., macrocephaly in deletion carriers (16pdel) and microcephaly in duplication carriers (16pdup). Using fibroblasts obtained from 16pdel and 16pdup carriers, we generated induced pluripotent stem cells (iPSCs) and differentiated them into neurons to identify causal cellular mechanisms underlying neurobiological phenotypes...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29212014/massive-and-reproducible-production-of-liver-buds-entirely-from-human-pluripotent-stem-cells
#14
Takanori Takebe, Keisuke Sekine, Masaki Kimura, Emi Yoshizawa, Satoru Ayano, Masaru Koido, Shizuka Funayama, Noriko Nakanishi, Tomoko Hisai, Tatsuya Kobayashi, Toshiharu Kasai, Rina Kitada, Akira Mori, Hiroaki Ayabe, Yoko Ejiri, Naoki Amimoto, Yosuke Yamazaki, Shimpei Ogawa, Momotaro Ishikawa, Yasujiro Kiyota, Yasuhiko Sato, Kohei Nozawa, Satoshi Okamoto, Yasuharu Ueno, Hideki Taniguchi
Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive "reverse" screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29212013/cell-type-of-origin-dictates-the-route-to-pluripotency
#15
Christian M Nefzger, Fernando J Rossello, Joseph Chen, Xiaodong Liu, Anja S Knaupp, Jaber Firas, Jacob M Paynter, Jahnvi Pflueger, Sam Buckberry, Sue Mei Lim, Brenda Williams, Sara Alaei, Keshav Faye-Chauhan, Enrico Petretto, Susan K Nilsson, Ryan Lister, Mirana Ramialison, David R Powell, Owen J L Rackham, Jose M Polo
Our current understanding of induced pluripotent stem cell (iPSC) generation has almost entirely been shaped by studies performed on reprogramming fibroblasts. However, whether the resulting model universally applies to the reprogramming process of other cell types is still largely unknown. By characterizing and profiling the reprogramming pathways of fibroblasts, neutrophils, and keratinocytes, we unveil that key events of the process, including loss of original cell identity, mesenchymal to epithelial transition, the extent of developmental reversion, and reactivation of the pluripotency network, are to a large degree cell-type specific...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29211687/cellular-reprogramming-dynamics-follow-a-simple-1d-reaction-coordinate
#16
Sai Teja Pusuluri, Alex H Lang, Pankaj Mehta, Horacio E Castillo
Cellular reprogramming, the conversion of one cell type to another, induces global changes in gene expression involving thousands of genes, and understanding how cells globally alter their gene expression profile during reprogramming is an ongoing problem. Here we reanalyze time-course data on cellular reprogramming from differentiated cell types to induced pluripotent stem cells (iPSCs) and show that gene expression dynamics during reprogramming follow a simple 1D reaction coordinate. This reaction coordinate is independent of both the time it takes to reach the iPSC state as well as the details of the experimental protocol used...
December 6, 2017: Physical Biology
https://www.readbyqxmd.com/read/29209912/restoration-of-smn-expression-in-mesenchymal-stem-cells-derived-from-gene-targeted-patient-specific-ipscs
#17
Mai Feng, Cong Liu, Yan Xia, Bo Liu, Miaojin Zhou, Zhuo Li, Qianru Sun, Zhiqing Hu, Yanchi Wang, Lingqian Wu, Xionghao Liu, Desheng Liang
Spinal muscular atrophy (SMA) is primarily a neurodegenerative disease caused by the homozygous deletion of the survival motor neuron 1 (SMN1) gene, thereby reducing SMN protein expression. Mesenchymal stem cells (MSCs) have been implicated in the treatment of SMA. In the present study, we overexpressed exogenous SMN1 at the ribosomal DNA (rDNA) locus of induced pluripotent stem cells (iPSCs) generated from a SMA patient using an rDNA-targeting vector. The gene-targeted patient iPSCs differentiated into MSCs (SMN1-MSCs)...
December 5, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29209158/induced-pluripotent-stem-cell-derived-neural-stem-cell-transplantations-reduced-behavioral-deficits-and-ameliorated-neuropathological-changes-in-yac128-mouse-model-of-huntington-s-disease
#18
Abeer Al-Gharaibeh, Rebecca Culver, Andrew N Stewart, Bhairavi Srinageshwar, Kristin Spelde, Laura Frollo, Nivya Kolli, Darren Story, Leela Paladugu, Sarah Anwar, Andrew Crane, Robert Wyse, Panchanan Maiti, Gary L Dunbar, Julien Rossignol
Huntington's disease (HD) is a genetic neurodegenerative disorder characterized by neuronal loss and motor dysfunction. Although there is no effective treatment, stem cell transplantation offers a promising therapeutic strategy, but the safety and efficacy of this approach needs to be optimized. The purpose of this study was to test the potential of intra-striatal transplantation of induced pluripotent stem cell-derived neural stem cells (iPS-NSCs) for treating HD. For this purpose, we developed mouse adenovirus-generated iPSCs, differentiated them into neural stem cells in vitro, labeled them with Hoechst, and transplanted them bilaterally into striata of 10-month old wild type (WT) and HD YAC128 mice...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29208628/impact-of-regulatory-variation-across-human-ipscs-and-differentiated-cells
#19
Nicholas E Banovich, Yang I Li, Anil Raj, Michelle C Ward, Peyton Greenside, Diego Calderon, Po-Yuan Tung, Jonathan E Burnett, Marsha Myrthil, Samantha M Thomas, Courtney K Burrows, Irene Gallego Romero, Bryan J Pavlovic, Anshul Kundaje, Jonathan K Pritchard, Yoav Gilad
Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. We investigated the use of iPSCs and iPSC- derived cells to study the impact of genetic variation on gene regulation across different cell types and as models for studies of complex disease. To do so, we established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes...
December 5, 2017: Genome Research
https://www.readbyqxmd.com/read/29207038/interaction-of-ipsc-derived-neural-stem-cells-on-poly-l-lactic-acid-nanofibrous-scaffolds-for-possible-use-in-neural-tissue-engineering
#20
Chengkai Lin, Chang Liu, Liangming Zhang, Zhi Huang, Peipei Zhao, Ruiqiang Chen, Mao Pang, Zhenxiang Chen, Liumin He, Chunxiao Luo, Limin Rong, Bin Liu
Tissue engineering is a rapidly growing technological area for the regeneration and reconstruction of damage to the central nervous system. By combining seed cells with appropriate biomaterial scaffolds, tissue engineering has the ability to improve nerve regeneration and functional recovery. In the present study, mouse induced pluripotent stem cells (iPSCs) were generated from mouse embryonic fibroblasts (MEFs) with the non-integrating episomal vectors pCEP4-EO2S-ET2K and pCEP4-miR-302-367 cluster, and differentiated into neural stem cells (NSCs) as transplanting cells...
November 30, 2017: International Journal of Molecular Medicine
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