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https://www.readbyqxmd.com/read/29779895/identification-and-single-cell-functional-characterization-of-an-endodermally-biased-pluripotent-substate-in-human-embryonic-stem-cells
#1
Thomas F Allison, Andrew J H Smith, Konstantinos Anastassiadis, Jackie Sloane-Stanley, Veronica Biga, Dylan Stavish, James Hackland, Shan Sabri, Justin Langerman, Mark Jones, Kathrin Plath, Daniel Coca, Ivana Barbaric, Paul Gokhale, Peter W Andrews
Human embryonic stem cells (hESCs) display substantial heterogeneity in gene expression, implying the existence of discrete substates within the stem cell compartment. To determine whether these substates impact fate decisions of hESCs we used a GFP reporter line to investigate the properties of fractions of putative undifferentiated cells defined by their differential expression of the endoderm transcription factor, GATA6, together with the hESC surface marker, SSEA3. By single-cell cloning, we confirmed that substates characterized by expression of GATA6 and SSEA3 include pluripotent stem cells capable of long-term self-renewal...
May 9, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29778942/transcriptomic-and-methylomic-analysis-reveal-the-toxicological-effect-of-2-3-7-8-tetrachlorodibenzodioxin-on-human-embryonic-stem-cell
#2
Keng Po Lai, Jing Woei Li, Ting Fung Chan, Andy Chen, Cherie Yin Lau Lee, William Shu Biu Yeung, Chris Kong Chu Wong
Cumulating epidemiological studies demonstrated that environmental exposure to endocrine disrupting chemicals (EDCs) during the early stages of fetal development is associated with the increase in disease susceptibility in later life. The fetal developmental plasticity is considered as a protective mechanism against an undesirable prenatal environment. Dioxin is one of the environmental contaminants and is considered a diabetogenic factor. Experimental animal and human epidemiological studies have revealed that dioxin exposure was associated with insulin resistance and altered beta cell function...
May 10, 2018: Chemosphere
https://www.readbyqxmd.com/read/29758359/probing-flecainide-block-of-i-na-using-human-pluripotent-stem-cell-derived-ventricular-cardiomyocytes-adapted-to-automated-patch-clamping-and-2d-monolayers
#3
Lin Geng, Chi-Wing Kong, Andy O T Won, Angie Man-Yee Shum, Maggie Z Y Chow, Hui Che, Chenzi Zhang, Ka-Long Yau, Camie W Chan, Wendy Keung, Ronald A Li
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are emerging tools for applications such as drug discovery and screening for pro-arrhythmogenicity and cardiotoxicity as leading causes for drug attrition. Understanding the electrophysiology (EP) of hPSC-CMs is essential but conventional manual patch-clamping is highly laborious and low-throughput. Here we adapted hPSC-CMs derived from two human embryonic stem cell (hESC) lines, HES2 and H7, for a 16-channel automated planar-recording approach for single-cell EP characterization...
May 11, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29758225/trpv6-protects-er-stress-induced-apoptosis-via-atf6%C3%AE-trpv6-jnk-pathway-in-human-embryonic-stem-cell-derived-cardiomyocytes
#4
Zhichao Li, Zhaoyue Meng, Jun Lu, Francis M Chen, Wing-Tak Wong, Gary Tse, Changbo Zheng, Wendy Keung, Kennis Tse, Ronald A Li, Liwen Jiang, Xiaoqiang Yao
Human pluripotent stem cell-derived cardiomyocytes have potential applications in disease modeling and drug screening. Therefore, it is important to understand the mechanisms and signaling pathways underlying the survival and death of these cells. Endoplasmic reticulum (ER) stress is triggered by various cellular stresses that disturb protein folding in the ER. Cells cope with ER stress by activating the unfolded protein response (UPR), a homeostatic signaling network that orchestrates the recovery of ER function...
May 11, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29755568/exosomes-secreted-by-normoxic-and-hypoxic-cardiosphere-derived-cells-have-anti-apoptotic-effect
#5
Helia Namazi, Iman Namazi, Parisa Ghiasi, Hassan Ansari, Sarah Rajabi, Ensiyeh Hajizadeh-Saffar, Nasser Aghdami, Elham Mohit
Cardiosphere-derived cells (CDCs) have emerged as one of the most promising stem cell types for cardiac protection and repair. Exosomes are required for the regenerative effects of human CDCs and mimic the cardioprotective benefits of CDCs such as anti-apoptotic effect in animal myocardial infarction (MI) models. Here we aimed to investigate the anti-apoptotic effect of the hypoxic and normoxic human CDCs-derived exosomes on induced apoptosis in human embryonic stem cell-derived cardiomyocytes (hESC-CMs). In this study, CDCs were cultured under normoxic (18% O2 ) and hypoxic (1% O2 ) conditions and CDC-exosomes were isolated from conditioned media by differential ultracentrifugation...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29755398/deconvolution-of-human-brain-cell-type-transcriptomes-unraveled-microglia-specific-potential-biomarkers
#6
R Ayana, Shailja Singh, Soumya Pati
Microglial cells form a context-dependent network of brain immunoeffector cells. Despite their indispensable roles, unresolved questions exist around biomarker discovery relevant to their cellular localization, self-renewing potential, and brain developmental dynamics. To resolve the existent gap in the annotation of candidate biomarkers, we conducted a meta-analysis of brain cells using available high-throughput data sets for deciphering microglia-specific expression profiles. We have identified 3,290 significant genes specific to microglia and further selected the top 20 dysregulated genes on the basis of p -value and log2 FC...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29751777/high-efficiency-derivation-of-human-embryonic-stem-cell-lines-using-a-culture-system-with-minimized-trophoblast-cell-proliferation
#7
Chuti Laowtammathron, Pimjai Chingsuwanrote, Roungsin Choavaratana, Suphadtra Phornwilardsiri, Ketsara Sitthirit, Chidchanok Kaewjunun, Orawan Makemaharn, Papussorn Terbto, Supaporn Waeteekul, Chanchao Lorthongpanich, Yaowalak U-Pratya, Pimonwan Srisook, Pakpoom Kheolamai, Surapol Issaragrisil
BACKGROUND: Due to their extensive self-renewal and multilineage differentiation capacity, human embryonic stem cells (hESCs) have great potential for studying developmental biology, disease modeling, and developing cell replacement therapy. The first hESC line was generated in 1998 by culturing inner cell mass (ICM) cells isolated from human blastocysts using an immunosurgery technique. Since then, many techniques including mechanical ICM isolation, laser dissection, and whole embryo culture have been used to derive hESC lines...
May 11, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29742390/20th-anniversary-of-isolation-of-human-embryonic-stem-cells-a-personal-perspective
#8
REVIEW
Joseph Itskovitz-Eldor
Following Jamie Thomson's lecture on primate embryonic stem cells (ESCs) at a meeting I had organized in March 1997, in Israel, to celebrate receipt of the Wolf Prize in Agriculture to my colleague and friend Neal First, frozen human embryos donated for research in Israel were shipped to Wisconsin. The five hESC lines (H1, H7, H9, H13, and H14) were established by early 1998 and transferred to my laboratory just before publication of their existence in Science, on November 6, 1998. The distribution of the cells from my institute to several laboratories, as early as 1999, enhanced the development of hESC research worldwide...
May 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29741810/quantitative-proteomics-study-reveals-changes-in-the-molecular-landscape-of-human-embryonic-stem-cells-with-impaired-stem-cell-differentiation-upon-exposure-to-titanium-dioxide-nanoparticles
#9
Lei Pan, Yew Mun Lee, Teck Kwang Lim, Qingsong Lin, Xiuqin Xu
The increasing number of nanoparticles (NPs) being used in various industries has led to growing concerns of potential hazards that NP exposure can incur on human health. However, its global effects on humans and the underlying mechanisms are not systemically studied. Human embryonic stem cells (hESCs), with the ability to differentiate to any cell types, provide a unique system to assess cellular, developmental, and functional toxicity in vitro within a single system highly relevant to human physiology. Here, the quantitative proteomics approach is adopted to evaluate the molecular consequences of titanium dioxide NPs (TiO2 NPs) exposure in hESCs...
May 9, 2018: Small
https://www.readbyqxmd.com/read/29734353/knockdown-of-cdk2ap1-in-human-embryonic-stem-cells-reduces-the-threshold-of-differentiation
#10
Khaled N Alsayegh, Steven D Sheridan, Shilpa Iyer, Raj Raghavendra Rao
Recent studies have suggested a role for the Cyclin Dependent Kinase-2 Associated Protein 1 (CDK2AP1) in stem cell differentiation and self-renewal. In studies with mouse embryonic stem cells (mESCs) derived from generated mice embryos with targeted deletion of the Cdk2ap1 gene, CDK2AP1 was shown to be required for epigenetic silencing of Oct4 during differentiation, with deletion resulting in persistent self-renewal and reduced differentiation potential. Differentiation capacity was restored in these cells following the introduction of a non-phosphorylatible form of the retinoblastoma protein (pRb) or exogenous Cdk2ap1...
2018: PloS One
https://www.readbyqxmd.com/read/29713018/a-pax5-oct4-prdm1-developmental-switch-specifies-human-primordial-germ-cells
#11
Fang Fang, Benjamin Angulo, Ninuo Xia, Meena Sukhwani, Zhengyuan Wang, Charles C Carey, Aurélien Mazurie, Jun Cui, Royce Wilkinson, Blake Wiedenheft, Naoko Irie, M Azim Surani, Kyle E Orwig, Renee A Reijo Pera
Dysregulation of genetic pathways during human germ cell development leads to infertility. Here, we analysed bona fide human primordial germ cells (hPGCs) to probe the developmental genetics of human germ cell specification and differentiation. We examined the distribution of OCT4 occupancy in hPGCs relative to human embryonic stem cells (hESCs). We demonstrated that development, from pluripotent stem cells to germ cells, is driven by switching partners with OCT4 from SOX2 to PAX5 and PRDM1. Gain- and loss-of-function studies revealed that PAX5 encodes a critical regulator of hPGC development...
April 30, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29712950/hsp90-inhibition-as-a-means-to-inhibit-activation-of-the-nlrp3-inflammasome
#12
Niina Piippo, Eveliina Korhonen, Maria Hytti, Heli Skottman, Kati Kinnunen, Natasha Josifovska, Goran Petrovski, Kai Kaarniranta, Anu Kauppinen
Once activated, the intracellular receptor NLRP3 assembles an inflammasome protein complex that facilitates the caspase-1-mediated maturation of IL-1β and IL-18. Inactive NLRP3 is guarded by a protein complex containing Hsp90. In response to stress stimuli, Hsp90 is released, and NLRP3 can be activated to promote inflammation. In this study, we blocked Hsp90 with geldanamycin and studied the fate of NLRP3 in human retinal pigment epithelial (RPE) cells. RPE cells play a central role in the development of age-related macular degeneration (AMD), a progressive eye disease causing severe vision loss in the elderly...
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29709474/keratinocyte-growth-factor-protects-endometrial-cells-from-oxygen-glucose-deprivation-re-oxygenation-via-activating-nrf2-signaling
#13
Xuting Shi, Hia-Yan Liu, Shu-Ping Li, Hong-Bin Xu
Oxygen and glucose deprivation (OGD)-re-oxygenation (OGDR) exposure to endometrial cells mimics ischemia-reperfusion injury. The present study tests the potential effect of keratinocyte growth factor (KGF) on the process. We show that KGF receptor KGFR is expressed in human endometrial T-HESC cells and primary murine endometrial cells. KGF pre-treatment protected endometrial cells from OGDR, inhibiting cell viability reduction and cell death. KGF attenuated OGDR-induced programmed necrosis in endometrial cells...
April 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29703701/robust-revascularization-in-models-of-limb-ischemia-using-a-clinically-translatable-human-stem-cell-derived-endothelial-cell-product
#14
Mark G MacAskill, Jaimy Saif, Alison Condie, Maurits A Jansen, Thomas J MacGillivray, Adriana A S Tavares, Lucija Fleisinger, Helen L Spencer, Marie Besnier, Ernesto Martin, Giovanni Biglino, David E Newby, Patrick W F Hadoke, Joanne C Mountford, Costanza Emanueli, Andrew H Baker
Pluripotent stem cell-derived differentiated endothelial cells offer high potential in regenerative medicine in the cardiovascular system. With the aim of translating the use of a human stem cell-derived endothelial cell product (hESC-ECP) for treatment of critical limb ischemia (CLI) in man, we report a good manufacturing practice (GMP)-compatible protocol and detailed cell tracking and efficacy data in multiple preclinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP, which was identified as mostly endothelial (60% CD31+ /CD144+ ), with the remainder of the subset expressing various pericyte/mesenchymal stem cell markers...
March 28, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29699383/human-embryonic-stem-cell-derived-from-early-stage-fertilized-ovum-non-immunogenic-and-universal-neuronal-and-non-neuronal-cell-lines
#15
Geeta Shroff, Arpita Srivastav, Rohan Shroff
Background: Human embryonic stem cells (hESCs) have the potential to treat various human disorders currently labeled as incurable and/or terminal illness. However, the fear that the patients' immune system would recognize them as non self and lead to an immune rejection has hampered their use. The main cause for immune rejection is usually the incompatibility of both donor and recipient's major histocompatibility complex (MHC). Methods: We describe a hESC line developed through a patented technology that does not lead to immune reaction upon transplantation...
April 30, 2018: International Journal of Stem Cells
https://www.readbyqxmd.com/read/29698509/microrna-425-and-microrna-155-cooperatively-regulate-atrial-natriuretic-peptide-expression-and-cgmp-production
#16
Sara Vandenwijngaert, Clara D Ledsky, Obiajulu Agha, Connie Wu, Dongjian Hu, Aranya Bagchi, Ibrahim J Domian, Emmanuel S Buys, Christopher Newton-Cheh, Donald B Bloch
AIMS: Atrial natriuretic peptide (ANP), secreted primarily by atrial cardiomyocytes, decreases blood pressure by raising cyclic 3',5'-guanosine monophosphate (cGMP) levels and inducing vasorelaxation, natriuresis, and diuresis. Raising the level of ANP has been shown to be an effective treatment for hypertension. To advance the future development of an anti-microRNA (miR) approach to increasing expression of ANP, we investigated the regulation of NPPA expression by two miRs: miR-425 and miR-155...
2018: PloS One
https://www.readbyqxmd.com/read/29696633/generation-of-reporter-hescs-by-targeting-egfp-at-the-cd144-locus-to-facilitate-the-endothelial-differentiation
#17
Zhiqing Hu, Yong Wu, Miaojin Zhou, Xiaolin Wang, Jialun Pang, Zhuo Li, Mai Feng, Yanchi Wang, Qian Hu, Junya Zhao, Xionghao Liu, Lingqian Wu, Desheng Liang
Reporter embryonic stem cell (ESC) lines with tissue-specific reporter genes may contribute to optimizing the differentiation conditions in vitro as well as trafficking transplanted cells in vivo. To optimize and monitor endothelial cell (EC) differentiation specifically, here we targeted the enhanced green fluorescent protein (EGFP) reporter gene at the junction of 5'UTR and exon2 of the endothelial specific marker gene CD144 using TALENs in human ESCs (H9) to generate a EGFP-CD144-reporter ESC line. The reporter cells expressed EGFP and CD144 increasingly and specifically without unexpected effects during the EC differentiation...
April 25, 2018: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/29696372/roles-of-autophagy-in-controlling-stem-cell-identity-a-perspective-of-self-renewal-and-differentiation
#18
REVIEW
Areechun Sotthibundhu, Wilasinee Promjuntuek, Min Liu, Sanbing Shen, Parinya Noisa
Autophagy is crucial for the removal of dysfunctional organelles and protein aggregates and for maintaining stem cell homeostasis, which includes self-renewal, cell differentiation and somatic reprogramming. Loss of self-renewal capacity and pluripotency is a major obstacle to stem cell-based therapies. It has been reported that autophagy regulates stem cells under biological stimuli, starvation, hypoxia, generation of reactive oxygen species (ROS) and cellular senescence. On the one hand, autophagy is shown to play roles in self-renewal by co-function with the ubiquitin-proteasome system (UPS) to promote pluripotency-associated proteins (NANOG, OCT4 and SOX2) in human embryonic stem cells (hESCs)...
April 25, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29693249/yes-associated-protein-mediates-human-embryonic-stem-cell-derived-cardiomyocyte-proliferation-involvement-of-epidermal-growth-factor-receptor-signaling
#19
Somi Park, Museog Choe, Hancheol Yeo, Hojae Han, Joongsun Kim, Woocheol Chang, Seungpil Yun, Hojin Lee, Minyoung Lee
Unlike mature cardiomyocytes, human pluripotent stem cell-derived cardiomyocytes exhibit higher proliferative capacity; however, the underlying mechanisms involved are yet to be elucidated. Here, we revealed that the Yes-associated protein (YAP) plays a critical role in regulating cell proliferation in association with epidermal growth factor receptor (EGFR) in human embryonic stem cell-derived cardiomyocytes (hESC-CMs). Our results show that low-density culture significantly promotes the proliferation of hESC-CMs via YAP...
April 25, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29686294/development-of-new-method-to-enrich-human-ipsc-derived-renal-progenitors-using-cell-surface-markers
#20
Azusa Hoshina, Tatsuya Kawamoto, Shin-Ichi Sueta, Shin-Ichi Mae, Toshikazu Araoka, Hiromi Tanaka, Yasunori Sato, Yukiko Yamagishi, Kenji Osafune
Cell therapy using renal progenitors differentiated from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) has the potential to significantly reduce the number of patients receiving dialysis therapy. However, the differentiation cultures may contain undifferentiated or undesired cell types that cause unwanted side effects, such as neoplastic formation, when transplanted into a body. Moreover, the hESCs/iPSCs are often genetically modified in order to isolate the derived renal progenitors, hampering clinical applications...
April 23, 2018: Scientific Reports
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