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Induced pluripotent stem cell

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https://www.readbyqxmd.com/read/28545230/nanog-plays-a-hierarchical-role-in-the-transcription-network-regulating-the-pluripotency-and-plasticity-of-adipose-tissue-derived-stem-cells
#1
Maria Pitrone, Giuseppe Pizzolanti, Laura Tomasello, Antonina Coppola, Lorenzo Morini, Gianni Pantuso, Romina Ficarella, Valentina Guarnotta, Sebastio Perrini, Francesco Giorgino, Carla Giordano
The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self-renewal potential and differentiation capacity. Our aim was to study the different expression of the embryonic stem cell markers NANOG (homeobox protein NANOG), SOX2 (SRY (sex determining region Y)-box 2) and OCT4 (octamer-binding transcription factor 4) and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28545044/differentiation-of-spontaneously-contracting-cardiomyocytes-from-non-virally-reprogrammed-human-amniotic-fluid-stem-cells
#2
Aaron J Velasquez-Mao, Christopher J M Tsao, Madeline N Monroe, Xavier Legras, Beatrice Bissig-Choisat, Karl-Dimiter Bissig, Rodrigo Ruano, Jeffrey G Jacot
Congenital heart defects are the most common birth defect. The limiting factor in tissue engineering repair strategies is an autologous source of functional cardiomyocytes. Amniotic fluid contains an ideal cell source for prenatal harvest and use in correction of congenital heart defects. This study aims to investigate the potential of amniotic fluid-derived stem cells (AFSC) to undergo non-viral reprogramming into induced pluripotent stem cells (iPSC) followed by growth-factor-free differentiation into functional cardiomyocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28544655/3d-bioprinting-human-induced-pluripotent-stem-cell-constructs-for-in-situ-cell-proliferation-and-successive-multilineage-differentiation
#3
Qi Gu, Eva Tomaskovic-Crook, Gordon G Wallace, Jeremy M Crook
The ability to create 3D tissues from induced pluripotent stem cells (iPSCs) is poised to revolutionize stem cell research and regenerative medicine, including individualized, patient-specific stem cell-based treatments. There are, however, few examples of tissue engineering using iPSCs. Their culture and differentiation is predominantly planar for monolayer cell support or induction of self-organizing embryoids (EBs) and organoids. Bioprinting iPSCs with advanced biomaterials promises to augment efforts to develop 3D tissues, ideally comprising direct-write printing of cells for encapsulation, proliferation, and differentiation...
May 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28544378/concise-review-induced-pluripotent-stem-cell-based-drug-discovery-for-mitochondrial-disease
#4
REVIEW
Gizem Inak, Carmen Lorenz, Pawel Lisowski, Annika Zink, Barbara Mlody, Alessandro Prigione
High attrition rates and loss of capital plague the drug discovery process. This is particularly evident for mitochondrial disease that typically involves neurological manifestations and is caused by nuclear or mitochondrial DNA defects. This group of heterogeneous disorders is difficult to target because of the variability of the symptoms among individual patients and the lack of viable modeling systems. The use of induced pluripotent stem cells (iPSCs) might significantly improve the search for effective therapies for mitochondrial disease...
May 22, 2017: Stem Cells
https://www.readbyqxmd.com/read/28544217/towards-a-crispr-picture-use-of-crispr-cas9-to-model-diseases-in-human-stem-cells-in-vitro
#5
Jamie L Freiermuth, Ian J Powell-Castilla, G Ian Gallicano
Human induced pluripotent stem cells (iPSCs) can be differentiated into any cell in the body unlocking enormous research potential. Combined with the recent discovery of CRISPR/Cas9 endonucleases in bacteria and their modification for use in biomedical research, these methods have the potential to revolutionize the field of genetic engineering and open the door to generating in vitro models that more closely resemble the in vivo system than ever before. Use of CRISPR/Cas9 has created a whirlwind within the scientific community in the last few years, as the race to move beyond just disease analysis and towards the goal of gene and cell therapy moves further...
May 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28543529/kir2-1-and-k2p1-channels-reconstitute-two-levels-of-resting-membrane-potential-in-cardiomyocytes
#6
Dongchuan Zuo, Kuihao Chen, Min Zhou, Zheng Liu, Haijun Chen
Strong inward rectifier K(+) (Kir2) channels primarily maintain normal resting membrane potential of cardiomyocytes. In sub-physiological extracellular K(+) concentrations or pathological hypokalaemia, human cardiomyocytes show both hyperpolarized and depolarized resting membrane potentials; these depolarized potentials cause cardiac arrhythmia; however, the underlying mechanism is unknown. Here we show that Kir2.1 currents non-linearly counterbalance hypokalaemia-induced K2P1 leak cation currents, reconstituting two levels of resting membrane potential in cardiomyocytes...
May 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28542487/characterization-of-micrornas-expression-profiles-in-human-dental-derived-pluripotent-stem-cells
#7
Xiaobing Tan, Qingyuan Dai
Induced pluripotent stem cells (iPSCs) technology provides a powerful means to generate and regenerate unlimited pluripotent stem cells directly from body tissue cells. Stem cells from apical papilla (SCAP) and Dental pulp stem cells (DPSCs) are present in 'cell-rich zones' within the dental pulp region, which are capable of regenerating pulp and dentin tissues in vivo. In this study, we investigated the difference of miRNAs expression in SCAPs and DPSCs before and after the reprogramming. Using miRNA microarray, 134 and 265 differentially expressed miRNAs in DPSCs- and SCAP-iPSCs were up-regulated compared to these before reprogramming...
2017: PloS One
https://www.readbyqxmd.com/read/28541509/evidence-that-phosphorylated-ubiquitin-signaling-is-involved-in-the-etiology-of-parkinson-s-disease
#8
Kahori Shiba-Fukushima, Kei-Ichi Ishikawa, Tsuyoshi Inoshita, Nana Izawa, Masashi Takanashi, Shigeto Sato, Osamu Onodera, Wado Akamatsu, Hideyuki Okano, Yuzuru Imai, Nobutaka Hattori
The ubiquitin (Ub) kinase PINK1 and the E3 Ub ligase Parkin, two gene products associated with young-onset Parkinson's disease (PD), participate in mitochondrial quality control. The phosphorylation of mitochondrial polyUb by PINK1, which is activated in a mitochondrial membrane potential (ΔΨm)-dependent manner, facilitates the mitochondrial translocation and concomitant enzymatic activation of Parkin, leading to the clearance of phospho-polyUb-tagged mitochondria via mitophagy. Thus, Ub phosphorylation is a key event in PINK1-Parkin-mediated mitophagy...
May 25, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28541275/engineering-the-haemogenic-niche-mitigates-endogenous-inhibitory-signals-and-controls-pluripotent-stem-cell-derived-blood-emergence
#9
Nafees Rahman, Patrick M Brauer, Lilian Ho, Tatiana Usenko, Mukul Tewary, Juan Carlos Zúñiga-Pflücker, Peter W Zandstra
Efforts to recapitulate haematopoiesis, a process guided by spatial and temporal inductive signals, to generate haematopoietic progenitors from human pluripotent stem cells (hPSCs) have focused primarily on exogenous signalling pathway activation or inhibition. Here we show haemogenic niches can be engineered using microfabrication strategies by micropatterning hPSC-derived haemogenic endothelial (HE) cells into spatially-organized, size-controlled colonies. CD34+VECAD+ HE cells were generated with multi-lineage potential in serum-free conditions and cultured as size-specific haemogenic niches that displayed enhanced blood cell induction over non-micropatterned cultures...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28541271/protein-altering-and-regulatory-genetic-variants-near-gata4-implicated-in-bicuspid-aortic-valve
#10
Bo Yang, Wei Zhou, Jiao Jiao, Jonas B Nielsen, Michael R Mathis, Mahyar Heydarpour, Guillaume Lettre, Lasse Folkersen, Siddharth Prakash, Claudia Schurmann, Lars Fritsche, Gregory A Farnum, Maoxuan Lin, Mohammad Othman, Whitney Hornsby, Anisa Driscoll, Alexandra Levasseur, Marc Thomas, Linda Farhat, Marie-Pierre Dubé, Eric M Isselbacher, Anders Franco-Cereceda, Dong-Chuan Guo, Erwin P Bottinger, G Michael Deeb, Anna Booher, Sachin Kheterpal, Y Eugene Chen, Hyun Min Kang, Jacob Kitzman, Heather J Cordell, Bernard D Keavney, Judith A Goodship, Santhi K Ganesh, Gonçalo Abecasis, Kim A Eagle, Alan P Boyle, Ruth J F Loos, Per Eriksson, Jean-Claude Tardif, Chad M Brummett, Dianna M Milewicz, Simon C Body, Cristen J Willer
Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28539972/site-specific-regulation-of-histone-h1-phosphorylation-in-pluripotent-cell-differentiation
#11
Ruiqi Liao, Craig A Mizzen
BACKGROUND: Structural variation among histone H1 variants confers distinct modes of chromatin binding that are important for differential regulation of chromatin condensation, gene expression and other processes. Changes in the expression and genomic distributions of H1 variants during cell differentiation appear to contribute to phenotypic differences between cell types, but few details are known about the roles of individual H1 variants and the significance of their disparate capacities for phosphorylation...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28539859/human-induced-pluripotent-stem-cells-generated-neural-cells-behaving-like-brain-and-spinal-cord-cells-an-insight-into-the-involvement-of-retinoic-acid-and-sonic-hedgehog-proteins
#12
Akinlolu Abdulazeez Adelaja
OBJECTIVES: The previous studies generated neural progenitor cells (NPCs) from human induced pluripotent stem cells (hiPSCs) using different protocols. However, the nature of the temporal or regional specificity of NPCs derived using these protocols is not well defined. Therefore, this study aimed to generate age- and region-specific NPCs from hiPSCs, which mimic in vivo fetal brain (FNPC-B) or spinal cord (FNPC-SC) tissues, in the absence or presence of retinoic acid (RA) and sonic hedgehog (SHH)...
April 2017: International Journal of Health Sciences
https://www.readbyqxmd.com/read/28539832/recapitulating-and-correcting-marfan-syndrome-in-a-cellular-model
#13
Jung Woo Park, Li Yan, Chris Stoddard, Xiaofang Wang, Zhichao Yue, Leann Crandall, Tiwanna Robinson, Yuxiao Chang, Kyle Denton, Enqin Li, Bin Jiang, Zhenwu Zhang, Kristen Martins-Taylor, Siu-Pok Yee, Hong Nie, Feng Gu, Wei Si, Ting Xie, Lixia Yue, Ren-He Xu
Marfan syndrome (MFS) is a connective tissue disorder caused by mutations in FBN1 gene, which encodes a key extracellular matrix protein FIBRILLIN-1. The haplosufficiency of FBN1 has been implicated in pathogenesis of MFS with manifestations primarily in cardiovascular, muscular, and ocular tissues. Due to limitations in animal models to study the late-onset diseases, human pluripotent stem cells (PSCs) offer a homogeneic tool for dissection of cellular and molecular pathogenic mechanism for MFS in vitro. Here, we first derived induced PSCs (iPSCs) from a MFS patient with a FBN1 mutation and corrected the mutation, thereby generating an isogenic "gain-of-function" control cells for the parental MFS iPSCs...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28539554/investigation-of-the-pathogenesis-of-autoimmune-diseases-by-ips-cells
#14
Bunki Natsumoto, Hirofumi Shoda, Keishi Fujio, Makoto Otsu, Kazuhiko Yamamoto
  The pluripotent stem cells have a self-renewal ability and can be differentiated into theoretically all of cell types. The induced pluripotent stem (iPS) cells overcame the ethical problems of the human embryonic stem (ES) cell, and enable pathologic analysis of intractable diseases and drug discovery. The in vitro disease model using disease-specific iPS cells enables repeated analyses of human cells without influence of environment factors. Even though autoimmune diseases are polygenic diseases, autoimmune disease-specific iPS cells are thought to be a promising tool for analyzing the pathogenesis of the diseases and drug discovery in future...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28539470/the-src-c-abl-pathway-is-a-potential-therapeutic-target-in-amyotrophic-lateral-sclerosis
#15
Keiko Imamura, Yuishin Izumi, Akira Watanabe, Kayoko Tsukita, Knut Woltjen, Takuya Yamamoto, Akitsu Hotta, Takayuki Kondo, Shiho Kitaoka, Akira Ohta, Akito Tanaka, Dai Watanabe, Mitsuya Morita, Hiroshi Takuma, Akira Tamaoka, Tilo Kunath, Selina Wray, Hirokazu Furuya, Takumi Era, Kouki Makioka, Koichi Okamoto, Takao Fujisawa, Hideki Nishitoh, Kengo Homma, Hidenori Ichijo, Jean-Pierre Julien, Nanako Obata, Masato Hosokawa, Haruhiko Akiyama, Satoshi Kaneko, Takashi Ayaki, Hidefumi Ito, Ryuji Kaji, Ryosuke Takahashi, Shinya Yamanaka, Haruhisa Inoue
Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment. We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout. Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1). Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway. Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28538216/the-emerging-view-of-aging-as-a-reversible-epigenetic-process
#16
Micaela López-León, Rodolfo G Goya
The achievement of animal cloning and subsequent development of cell reprogramming technology are having a profound impact on our view of the mechanisms of aging in complex organisms. The experimental evidence showing that an adult somatic nucleus implanted into an enucleated oocyte can give rise to a whole new individual strongly suggests that the integrity of the genome of an adult nucleus is fully preserved. Here, we will review recent experimental evidence showing that pluripotency gene-based cell reprogramming can erase the epigenetic marks of aging and rejuvenate cells from old individuals reversing most signs of aging and that when induced pluripotent stem cells are differentiated back to the cell type of origin, the rejuvenated cells share many of the features of wild-type counterparts from young donors...
May 25, 2017: Gerontology
https://www.readbyqxmd.com/read/28537559/enforcement-of-developmental-lineage-specificity-by-transcription-factor-oct1
#17
Zuolian Shen, Jinsuk Kang, Arvind Shakya, Marcin Tabaka, Elke A Jarboe, Aviv Regev, Dean Tantin
Embryonic stem cells co-express Oct4 and Oct1, a related protein with similar DNA binding specificity. To study the role of Oct1 in ESC pluripotency and transcriptional control, we constructed germline and inducible-conditional Oct1 deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal and growth, but manifest defects upon differentiation. They fail to form beating cardiomyocytes, generate neurons poorly, form small, poorly differentiated teratomas, and cannot generate chimeric mice. Upon RA-mediated differentiation, Oct1 deficient cells induce lineage-appropriate developmentally poised genes poorly while lineage-inappropriate genes, including extra-embryonic genes, are inappropriately expressed...
May 24, 2017: ELife
https://www.readbyqxmd.com/read/28537488/capturing-human-na%C3%A3-ve-pluripotency-in-the-embryo-and-in-the-dish
#18
Ludovic Zimmerlin, Tea Soon Park, Elias T Zambidis
Although human embryonic stem cells (hESC) were first derived almost 20 years ago, it was only recently acknowledged that they share closer molecular and functional identity to post-implantation lineage-primed murine epiblast stem cells (EpiSC) than to naïve pre-implantation ICM-derived mouse embryonic stem cells (ESC). A myriad of transcriptional, epigenetic, biochemical, and metabolic attributes have now been described that distinguish naïve and primed pluripotent states in both rodents and humans. Conventional hESC and human induced pluripotent stem cells (hiPSC) appear to lack many of the defining hallmarks of naïve mouse ESC...
May 24, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28536890/progress-and-future-prospectives-in-skin-on-chip-development-with-emphasis-on-the-use-of-different-cell-types-and-technical-challenges
#19
Lenie J van den Broek, Lambert I J C Bergers, Christianne M A Reijnders, Susan Gibbs
Understanding the healthy and diseased state of skin is important in many areas of basic and applied research. Although the field of skin tissue engineering has advanced greatly over the last years, current in vitro skin models still do not mimic the complexity of the human skin. Skin-on-chip and induced pluripotent stem cells (iPSC) might be key technologies to improve in vitro skin models. This review summarizes the state of the art of in vitro skin models with regard to cell sources (primary, cell line, iPSC) and microfluidic devices...
May 24, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28536871/impact-of-early-subcultures-on-stemness-migration-and-angiogenic-potential-of-adipose-tissue-derived-stem-cells-and-their-resistance-to-in-vitro-ischemic-condition
#20
Hossein Faghih, Arash Javeri, Masoumeh Fakhr Taha
Adipose tissue-derived stem cells (ADSCs) are capable of multipotential differentiation and express several angiogenic, anti-apoptotic and immunomodulatory markers. These features make adipose tissue as a promising source of stem cells for regenerative medicine. However, for efficient translational use, culture-induced changes in the gene expression profile and resistance of the ADSCs to ischemic environment should be taken into consideration. We compared the expression of some clinically important markers between the unpassaged and third-passaged ADSCs by RT-PCR, qPCR and flow cytometry...
May 23, 2017: Cytotechnology
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