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https://www.readbyqxmd.com/read/28527889/enhanced-cardiomyogenic-induction-of-mouse-pluripotent-cells-by-cyclic-mechanical-stretch
#1
Akankshya Shradhanjali, Brandon D Riehl, Jeong Soon Lee, Ligyeom Ha, Jung Yul Lim
The cardiac milieu is mechanically active with spontaneous contraction beginning from early development and persistent through maturation and homeostasis, suggesting that mechanical loading may provide biomimetic myocardial developmental signal. In this study, we tested the role of cyclic mechanical stretch loading in the cardiomyogenesis of pluripotent murine embryonic (P19) stem cells. A Flexcell tension system was utilized to apply equiaxial stretch (12% strain, 1.25 Hz frequency) to P19 cell-derived embryoid bodies (EBs)...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526606/identification-of-emsox2-a-member-of-the-sox-family-of-transcription-factors-as-a-potential-regulator-of-echinococcus-multilocularis-germinative-cells
#2
Zhe Cheng, Fan Liu, Mengya Dai, Jianjian Wu, Xiu Li, Xinrui Guo, Huimin Tian, Zhijie Heng, Ying Lu, Xiaoli Chai, Yanhai Wang
Larvae of the tapeworm Echinococcus multilocularis cause alveolar echinococcosis (AE), one of the most lethal helminthic infections in humans. The germinative cells, a population of stem cell-like cells, are considered to drive the continuous growth of the metacestodes within the host. The mechanisms and relative molecules controlling the behavior of germinative cells are poorly understood. Sox transcription factors play important roles in maintenance and regulation of stem/progenitor cells. We here describe the identification of a Sox family member in E...
May 16, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28526555/modeling-psychomotor-retardation-using-ipscs-from-mct8-deficient-patients-indicates-a-prominent-role-for-the-blood-brain-barrier
#3
Gad D Vatine, Abraham Al-Ahmad, Bianca K Barriga, Soshana Svendsen, Ariel Salim, Leslie Garcia, Veronica J Garcia, Ritchie Ho, Nur Yucer, Tongcheng Qian, Ryan G Lim, Jie Wu, Leslie M Thompson, Weston R Spivia, Zhaohui Chen, Jennifer Van Eyk, Sean P Palecek, Samuel Refetoff, Eric V Shusta, Clive N Svendsen
Inactivating mutations in the thyroid hormone (TH) transporter Monocarboxylate transporter 8 (MCT8) cause severe psychomotor retardation in children. Animal models do not reflect the biology of the human disease. Using patient-specific induced pluripotent stem cells (iPSCs), we generated MCT8-deficient neural cells that showed normal TH-dependent neuronal properties and maturation. However, the blood-brain barrier (BBB) controls TH entry into the brain, and reduced TH availability to neural cells could instead underlie the diseased phenotype...
May 8, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28526246/impaired-mitophagy-facilitates-mitochondrial-damage-in-danon-disease
#4
Sherin I Hashem, Anne N Murphy, Ajit S Divakaruni, Matthew L Klos, Bradley C Nelson, Emily C Gault, Teisha J Rowland, Cynthia N Perry, Yusu Gu, Nancy D Dalton, William H Bradford, Eric J Devaney, Kirk L Peterson, Kenneth L Jones, Matthew R G Taylor, Ju Chen, Neil C Chi, Eric D Adler
RATIONALE: Lysosomal associated membrane protein type-2 (LAMP-2) is a highly conserved, ubiquitous protein that is critical for autophagic flux. Loss of function mutations in the LAMP-2 gene cause Danon disease, a rare X-linked disorder characterized by developmental delay, skeletal muscle weakness, and severe cardiomyopathy. We previously found that human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from Danon patients exhibited significant mitochondrial oxidative stress and apoptosis...
May 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28525643/synthetic-mrna-devices-that-detect-endogenous-proteins-and-distinguish-mammalian-cells
#5
Shunsuke Kawasaki, Yoshihiko Fujita, Takashi Nagaike, Kozo Tomita, Hirohide Saito
Synthetic biology has great potential for future therapeutic applications including autonomous cell programming through the detection of protein signals and the production of desired outputs. Synthetic RNA devices are promising for this purpose. However, the number of available devices is limited due to the difficulty in the detection of endogenous proteins within a cell. Here, we show a strategy to construct synthetic mRNA devices that detect endogenous proteins in living cells, control translation and distinguish cell types...
May 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28525578/cell-type-specific-genome-editing-with-a-microrna-responsive-crispr-cas9-switch
#6
Moe Hirosawa, Yoshihiko Fujita, Callum J C Parr, Karin Hayashi, Shunnichi Kashida, Akitsu Hotta, Knut Woltjen, Hirohide Saito
The CRISPR-Cas9 system is a powerful genome-editing tool useful in a variety of biotechnology and biomedical applications. Here we developed a synthetic RNA-based, microRNA (miRNA)-responsive CRISPR-Cas9 system (miR-Cas9 switch) in which the genome editing activity of Cas9 can be modulated through endogenous miRNA signatures in mammalian cells. We created miR-Cas9 switches by using a miRNA-complementary sequence in the 5΄-UTR of mRNA encoding Streptococcus pyogenes Cas9. The miR-21-Cas9 or miR-302-Cas9 switches selectively and efficiently responded to miR-21-5p in HeLa cells or miR-302a-5p in human induced pluripotent stem cells, and post-transcriptionally attenuated the Cas9 activity only in the target cells...
May 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28525289/high-throughput-phenotyping-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-and-neurons-using-electric-field-stimulation-and-high-speed-fluorescence-imaging
#7
Neil J Daily, Zhong-Wei Du, Tetsuro Wakatsuki
Electrophysiology of excitable cells, including muscle cells and neurons, has been measured by making direct contact with a single cell using a micropipette electrode. To increase the assay throughput, optical devices such as microscopes and microplate readers have been used to analyze electrophysiology of multiple cells. We have established a high-throughput (HTP) analysis of action potentials (APs) in highly enriched motor neurons and cardiomyocytes (CMs) that are differentiated from human induced pluripotent stem cells (iPSCs)...
May 19, 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28524367/transplantation-of-human-villous-trophoblasts-preserves-cardiac-function-in-mice-with-acute-myocardial-infarction
#8
Zegen Wang, Ningzheng Dong, Yayan Niu, Zhiwei Zhang, Ce Zhang, Meng Liu, Tiantian Zhou, Qingyu Wu, Ke Cheng
Over the past decade, cell therapies have provided promising strategies for the treatment of ischaemic cardiomyopathy. Particularly, the beneficial effects of stem cells, including bone marrow stem cells (BMSCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), have been demonstrated by substantial preclinical and clinical studies. Nevertheless stem cell therapy is not always safe and effective. Hence, there is an urgent need for alternative sources of cells to promote cardiac regeneration...
May 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28522326/gene-editing-and-clonal-isolation-of-human-induced-pluripotent-stem-cells-using-crispr-cas9
#9
Saniye Yumlu, Jürgen Stumm, Sanum Bashir, Anne-Kathrin Dreyer, Pawel Lisowski, Eric Danner, Ralf Kühn
Human induced pluripotent stem cells (hiPSCs) represent an ideal in vitro platform to study human genetics and biology. The recent advent of programmable nucleases makes also the human genome amenable to experimental genetics through either the correction of mutations in patient-derived iPSC lines or the de novo introduction of mutations into otherwise healthy iPSCs. The production of specific and sometimes complex genotypes in multiple cell lines requires efficient and streamlined gene editing technologies...
May 15, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28521042/induced-pluripotent-stem-cell-modelling-of-hlhs-underlines-the-contribution-of-dysfunctional-notch-signalling-to-impaired-cardiogenesis
#10
Chunbo Yang, Yaobo Xu, Min Yu, David Lee, Sameer Alharti, Nicola Hellen, Noor Ahmad Shaik, Babajan Banaganapalli, Hussein Ali Mohamoud Sheikh, Elango Ramu, Stefan Przyborski, Gennadiy Tenin, Simon Williams, John O'Sullivan, Osman O Al-Radi, Jameel Atta, Sian E Harding, Bernard Keavney, Majlinda Lako, Lyle Armstrong
Hypoplastic left heart syndrome (HLHS) is among the most severe forms of congenital heart disease. Although the consensus view is that reduced flow through the left heart during development is a key factor in the development of the condition, the molecular mechanisms leading to hypoplasia of left heart structures are unknown. We have generated induced pluripotent stem cells (iPSC) from five HLHS patients and two unaffected controls, differentiated these to cardiomyocytes and identified reproducible in vitro cellular and functional correlates of the HLHS phenotype...
May 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28521025/mechanism-of-as2o3-induced-action-potential-prolongation-and-using-hips-cms-to-evaluate-the-rescue-efficacy-of-drugs-with-different-rescue-mechanism
#11
Meng Yan, Lifang Feng, Yanhui Shi, Junnan Wang, Yan Liu, Fengmei Li, Baoxin Li
Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28520591/stem-cell-therapy-and-its-potential-role-in-pituitary-disorders
#12
Montserrat Lara-Velazquez, Akinduro O Oluwaseun, Ronald Reimer, Whitney W Woodmansee, Alfredo Quinones-Hinojosa
PURPOSE OF REVIEW: The pituitary gland is one of the key components of the endocrine system. Congenital or acquired alterations can mediate destruction of cells in the gland leading to hormonal dysfunction. Even though pharmacological treatment for pituitary disorders is available, exogenous hormone replacement is neither curative nor sustainable. Thus, alternative therapies to optimize management and improve quality of life are desired. RECENT FINDINGS: An alternative modality to re-establish pituitary function is to promote endocrine cell regeneration through stem cells that can be obtained from the pituitary parenchyma or pluripotent cells...
May 16, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28520534/cpg-island-methylation-correlates-with-the-use-of-alternative-promoter-for-usp44-gene-expression-in-human-pluripotent-stem-cells-and-testis
#13
Philippe Tropel, Laura Jung, Cécile André, Adeline Ndandougou, Stéphane Viville
Deubiquitinating enzymes may play a major regulatory role in pluripotent stem cells (PSCs) but few studies have investigated this topic. Within this family of enzymes, we found that the ubiquitin specific peptidase, USP44, is highly expressed in embryonic stem cells, induced PSCs and testes as compared to differentiated progenies and somatic organs. Analysis by qPCR and 5'RACE showed that alternate promoters are responsible for expression in PSCs and organs. We noticed 7 regions of transcription initiation, some of them with cell- or tissue-specific activity...
May 18, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28520232/human-ipsc-msc-derived-xenografts-modulate-immune-responses-by-inhibiting-the-cleavage-of-caspases
#14
Cheng-Lin Li, Yun Leng, Bin Zhao, Chang Gao, Fei-Fei Du, Ning Jin, Qi-Zhou Lian, Shuang-Yue Xu, Guo-Liang Yan, Jun-Jie Xia, Guo-Hong Zhuang, Qing-Ling Fu, Zhong-Quan Qi
Mesenchymal stem cells (MSCs) negatively modulate immune properties. Induced pluripotent stem cells (iPSCs)-derived MSCs are alternative source of MSCs. However, the effects of iPSC-MSCs on T cells phenotypes in vivo remain unclear. We established an iPSC-MSC-transplanted host versus graft reaction mouse model using subcapsular kidney injection. Th1, Th2, regulatory T cells (Treg), and Th17 phenotypes and their cytokines were investigated in vivo and in vitro. The role of caspases and the soluble factors involved in the effects of MSCs were examined...
May 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28518082/maturation-of-human-stem-cell-derived-cardiomyocytes-in-biowires-using-electrical-stimulation
#15
Xuetao Sun, Sara S Nunes
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been a promising cell source and have thus encouraged the investigation of their potential applications in cardiac research, including drug discovery, disease modeling, tissue engineering, and regenerative medicine. However, cells produced by existing protocols display a range of immaturity compared with native adult ventricular cardiomyocytes. Many efforts have been made to mature hPSC-CMs, with only moderate maturation attained thus far. Therefore, an engineered system, called biowire, has been devised by providing both physical and electrical cues to lead hPSC-CMs to a more mature state in vitro...
May 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28515341/bet-bromodomain-inhibition-suppresses-innate-inflammatory-and-profibrotic-transcriptional-networks-in-heart-failure
#16
Qiming Duan, Sarah McMahon, Priti Anand, Hirsh Shah, Sean Thomas, Hazel T Salunga, Yu Huang, Rongli Zhang, Aarathi Sahadevan, Madeleine E Lemieux, Jonathan D Brown, Deepak Srivastava, James E Bradner, Timothy A McKinsey, Saptarsi M Haldar
Despite current standard of care, the average 5-year mortality after an initial diagnosis of heart failure (HF) is about 40%, reflecting an urgent need for new therapeutic approaches. Previous studies demonstrated that the epigenetic reader protein bromodomain-containing protein 4 (BRD4), an emerging therapeutic target in cancer, functions as a critical coactivator of pathologic gene transactivation during cardiomyocyte hypertrophy. However, the therapeutic relevance of these findings to human disease remained unknown...
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28514664/lack-of-mttp-activity-in-pluripotent-stem-cell-derived-hepatocytes-and-cardiomyocytes-abolishes-apob-secretion-and-increases-cell-stress
#17
Ying Liu, Donna M Conlon, Xin Bi, Katherine J Slovik, Jianting Shi, Hailey I Edelstein, John S Millar, Ali Javaheri, Marina Cuchel, Evanthia E Pashos, Jahangir Iqbal, M Mahmood Hussain, Robert A Hegele, Wenli Yang, Stephen A Duncan, Daniel J Rader, Edward E Morrisey
Abetalipoproteinemia (ABL) is an inherited disorder of lipoprotein metabolism resulting from mutations in microsomal triglyceride transfer protein (MTTP). In addition to expression in the liver and intestine, MTTP is expressed in cardiomyocytes, and cardiomyopathy has been reported in several ABL cases. Using induced pluripotent stem cells (iPSCs) generated from an ABL patient homozygous for a missense mutation (MTTP(R46G)), we show that human hepatocytes and cardiomyocytes exhibit defects associated with ABL disease, including loss of apolipoprotein B (apoB) secretion and intracellular accumulation of lipids...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28514657/huntington-s-disease-ipsc-derived-brain-microvascular-endothelial-cells-reveal-wnt-mediated-angiogenic-and-blood-brain-barrier-deficits
#18
Ryan G Lim, Chris Quan, Andrea M Reyes-Ortiz, Sarah E Lutz, Amanda J Kedaigle, Theresa A Gipson, Jie Wu, Gad D Vatine, Jennifer Stocksdale, Malcolm S Casale, Clive N Svendsen, Ernest Fraenkel, David E Housman, Dritan Agalliu, Leslie M Thompson
Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28514649/widespread-mitotic-bookmarking-by-histone-marks-and-transcription-factors-in-pluripotent-stem-cells
#19
Yiyuan Liu, Bobbie Pelham-Webb, Dafne Campigli Di Giammartino, Jiexi Li, Daleum Kim, Katsuhiro Kita, Nestor Saiz, Vidur Garg, Ashley Doane, Paraskevi Giannakakou, Anna-Katerina Hadjantonakis, Olivier Elemento, Effie Apostolou
During mitosis, transcription is halted and many chromatin features are lost, posing a challenge for the continuity of cell identity, particularly in fast cycling stem cells, which constantly balance self-renewal with differentiation. Here we show that, in pluripotent stem cells, certain histone marks and stem cell regulators remain associated with specific genomic regions of mitotic chromatin, a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes are bookmarked by both H3K27ac and the master regulators OCT4, SOX2, and KLF4, while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a cell-type invariant manner...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28514439/haematopoietic-stem-and-progenitor-cells-from-human-pluripotent-stem-cells
#20
Ryohichi Sugimura, Deepak Kumar Jha, Areum Han, Clara Soria-Valles, Edroaldo Lummertz da Rocha, Yi-Fen Lu, Jeremy A Goettel, Erik Serrao, R Grant Rowe, Mohan Malleshaiah, Irene Wong, Patricia Sousa, Ted N Zhu, Andrea Ditadi, Gordon Keller, Alan N Engelman, Scott B Snapper, Sergei Doulatov, George Q Daley
A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts...
May 17, 2017: Nature
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