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Induced pluripotent stem cells

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https://www.readbyqxmd.com/read/29222839/decellularized-human-liver-extracellular-matrix-hdlm-mediated-hepatic-differentiation-of-human-induced-pluripotent-stem-cells-hipsc
#1
Maria Jaramillo, Heidi Yeh, Martin L Yarmush, Basak E Uygun
Liver tissue engineering has emerged as a promising approach in organ transplantation, but has been hampered by the lack of a reliable and readily available cell source. Induced pluripotent cells (hiPSC) have been highlighted a desirable source, due to their differentiation potential, ability to self-renew and the possibility of making patient specific cells. We developed a decellularization protocol that efficiently removes cellular material, while retaining extracellular matrix components. Subsequently, hiPSC were differentiated on the decellularized human liver matrix (hDLM) scaffolds using an established hepatic differentiation protocol...
December 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29222327/mitochondrially-produced-atp-affects-stem-cell-pluripotency-via-actl6a-mediated-histone-acetylation
#2
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
#3
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/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/29220659/organizing-organoids-stem-cells-branch-out
#5
Jamie A Davies
In this issue of Cell Stem Cell, Taguchi and Nishinakamura (2017) describe a carefully optimized method for making a branch-competent ureteric bud, a tissue fundamental to kidney development, from mouse embryonic stem cells and human induced pluripotent stem cells. The work illuminates embryology and has important implications for making more realistic kidney organoids.
December 7, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29218329/high-mobility-group-protein-2-regulated-by-microrna-127-and-small-heterodimer-partner-modulates-pluripotency-of-mouse-embryonic-stem-cells-and-liver-tumor-initiating-cells
#6
Yulan Zhao, Zhihong Yang, Jianguo Wu, Raymond Wu, Santosh K Keshipeddy, Dennis Wright, Li Wang
High-mobility-group protein 2 (HMGB2) expression is upregulated in human liver cancer. However, little is known about its regulatory function. Here we establish HMGB2 as a new modulator of the pluripotency of mouse embryonic stem cells (ESCs). Similar to OCT4 and SOX2, HMGB2 protein is highly expressed in undifferentiated CGR8 cells, whereas it undergoes rapid decline during embryonic body (EB) formation. HMGB2 interacts with OCT4, increases protein expression of OCT4 and SOX2, and enhances their transcriptional activities...
October 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29217999/prospects-for-modeling-abnormal-neuronal-function-in-schizophrenia-using-human-induced-pluripotent-stem-cells
#7
REVIEW
Iya Prytkova, Kristen J Brennand
Excitatory dopaminergic neurons, inhibitory GABAergic neurons, microglia, and oligodendrocytes have all been implicated in schizophrenia (SZ) network pathology. Still, SZ has been a difficult disorder to study, not only because of the limitations of animal models in capturing the complexity of the human mind, but also because it is greatly polygenic, with high rates of variability across the population. The advent of patient-derived pluripotent stem cells and induced neural and glial cultures has brought hope for modeling the molecular dysfunction underlying SZ pathology in a patient-specific manner...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29217756/light-focusing-human-micro-lenses-derived-from-zebrafish-like-lens-cell-masses-model-lens-development-and-drug-induced-cataract-in-vitro
#8
Patricia Murphy, Md Humayun Kabir, Tarini Srivastava, Michele E Mason, Chitra Umala Dewi, Seakcheng Lim, Andrian Yang, Djordje Djordjevic, Murray C Killingsworth, Joshua W K Ho, David G Harman, Michael D O'Connor
Cataracts cause vision loss and blindness by impairing the ability of the ocular lens to focus light onto the retina. Various cataract risk factors have been identified including drug treatments, age, smoking, and diabetes. However, the molecular events responsible for these different forms of cataract are ill-defined, and the advent of modern cataract surgery in the 1960s virtually eliminated access to human lenses for research. Here we demonstrate large-scale production of light-focusing human micro-lenses from spheroidal masses of human lens epithelial cells purified from differentiating pluripotent stem cells...
December 7, 2017: Development
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
#9
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/29217200/timing-is-everything-reiterative-wnt-bmp-and-ra-signaling-regulate-developmental-competence-during-endoderm-organogenesis
#10
Scott A Rankin, Kyle W McCracken, David M Luedeke, Lu Han, James M Wells, John M Shannon, Aaron M Zorn
A small number of signaling pathways are used repeatedly during organogenesis, and they can have drastically different effects on the same population of cells depending on the embryonic stage. How cellular competence changes over developmental time is not well understood. Here we used Xenopus, mouse, and human pluripotent stem cells to investigate how the temporal sequence of Wnt, BMP, and retinoic acid (RA) signals regulates endoderm developmental competence and organ induction, focusing on respiratory fate...
December 4, 2017: Developmental Biology
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
#11
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
#12
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/29216542/loss-of-heme-oxygenase-1-accelerates-mesodermal-gene-expressions-during-embryoid-body-development-from-mouse-embryonic-stem-cells
#13
Yan-Liang Lai, Chen-Yu Lin, Wei-Cheng Jiang, Yen-Chun Ho, Chung-Huang Chen, Shaw-Fang Yet
Heme oxygenase (HO)-1 is an inducible stress response protein and well known to protect cells and tissues against injury. Despite its important function in cytoprotection against physiological stress, the role of HO-1 in embryonic stem cell (ESC) differentiation remains largely unknown. We showed previously that induced pluripotent stem (iPS) cells that lack HO-1 are more sensitive to oxidant stress-induced cell death and more prone to lose pluripotent markers upon LIF withdrawal. To elucidate the role of HO-1 in ESC differentiation and to rule out the controversy of potential gene flaws in iPS cells, we derived and established mouse HO-1 knockout ESC lines from HO-1 knockout blastocysts...
November 22, 2017: Redox Biology
https://www.readbyqxmd.com/read/29215942/cocktail-of-chemical-compounds-and-recombinant-proteins-robustly-promote-the-stemness-of-adipose-derived-stem-cells
#14
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/29215199/neurotrophically-induced-mesenchymal-progenitor-cells-derived-from-induced-pluripotent-stem-cells-enhance-neuritogenesis-via-neurotrophin-and-cytokine-production
#15
Rachel M Brick, Aaron X Sun, Rocky S Tuan
Adult tissue-derived mesenchymal stem cells (MSCs) are known to produce a number of bioactive factors, including neurotrophic growth factors, capable of supporting and improving nerve regeneration. However, with a finite culture expansion capacity, MSCs are inherently limited in their lifespan and use. We examined here the potential utility of an alternative, mesenchymal-like cell source, derived from induced pluripotent stem cells, termed induced mesenchymal progenitor cells (MiMPCs). We found that several genes were upregulated and proteins were produced in MiMPCs that matched those previously reported for MSCs...
December 7, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29214996/the-role-of-cdx2-as-a-lineage-specific-transcriptional-repressor-for-pluripotent-network-during-the-first-developmental-cell-lineage-segregation
#16
Daosheng Huang, Guoji Guo, Ping Yuan, Amy Ralston, Lingang Sun, Mikael Huss, Tapan Mistri, Luca Pinello, Huck Hui Ng, Guocheng Yuan, Junfeng Ji, Janet Rossant, Paul Robson, Xiaoping Han
The first cellular differentiation event in mouse development leads to the formation of the blastocyst consisting of the inner cell mass (ICM) and trophectoderm (TE). The transcription factor CDX2 is required for proper TE specification, where it promotes expression of TE genes, and represses expression of Pou5f1 (OCT4). However its downstream network in the developing embryo is not fully characterized. Here, we performed high-throughput single embryo qPCR analysis in Cdx2 null embryos to identify CDX2-regulated targets in vivo...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212799/lif-activated-jak-signaling-determines-esrrb-expression-during-late-stage-reprogramming
#17
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/29212797/in-vitro-and-in-vivo-differentiation-of-induced-pluripotent-stem-cells-generated-from-urine-derived-cells-into-cardiomyocytes
#18
Yu-Feng Jiang, Min Chen, Nan-Nan Zhang, Hua-Jia Yang, Qing Rui, Ya-Feng Zhou
Breakthrough advances in stem cell research made it possible for generation of human cardiomyocytes from cells derived from various sources, including skin biopsy. However, it is attractive to build up a negligibly invasive way to create induced pluripotent stem (iPS) cells. In this study, we created iPS cells from human urine-derived epithelial cells by gene transduction using lentiviral vectors in a totally noninvasive manner. After that, we induced the differentiation of iPS cells into functional cardiomyocytes both in vitro and in vivo Action potentials were recorded in putative cardiomyocytes and spontaneous beating cells were observed...
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
#19
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
#20
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
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