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Stem Cell Reports

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https://www.readbyqxmd.com/read/28735850/enhanced-energetic-state-and-protection-from-oxidative-stress-in-human-myoblasts-overexpressing-bmi1
#1
Silvia Dibenedetto, Maria Niklison-Chirou, Claudia P Cabrera, Matthew Ellis, Lesley G Robson, Paul Knopp, Francesco Saverio Tedesco, Martina Ragazzi, Valentina Di Foggia, Michael R Barnes, Aleksandar Radunovic, Silvia Marino
The Polycomb group gene BMI1 is essential for efficient muscle regeneration in a mouse model of Duchenne muscular dystrophy, and its enhanced expression in adult skeletal muscle satellite cells ameliorates the muscle strength in this model. Here, we show that the impact of mild BMI1 overexpression observed in mouse models is translatable to human cells. In human myoblasts, BMI1 overexpression increases mitochondrial activity, leading to an enhanced energetic state with increased ATP production and concomitant protection against DNA damage both in vitro and upon xenografting in a severe dystrophic mouse model...
July 17, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28689995/sirt1-enhances-the-survival-of-human-embryonic-stem-cells-by-promoting-dna-repair
#2
Jiho Jang, Yong Jun Huh, Hyun-Ju Cho, Boram Lee, Jaepil Park, Dong-Youn Hwang, Dong-Wook Kim
Human embryonic stem cells (hESCs) hold great promise for the treatment of many incurable diseases. Sirtuin1 (SIRT1), a class III histone deacetylase, is abundantly expressed in hESCs and is known to regulate early differentiation and telomere elongation. Here, we show that downregulation of SIRT1 promotes cell death in hESCs, but not in differentiated cells, and the SIRT1-inhibition-mediated cell death is preceded by increased DNA damage. This increased DNA damage is at least partially due to decreased levels of DNA repair enzymes such as MSH2, MSH6, and APEX1...
July 5, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28689996/adult-mouse-liver-contains-two-distinct-populations-of-cholangiocytes
#3
Bin Li, Craig Dorrell, Pamela S Canaday, Carl Pelz, Annelise Haft, Milton Finegold, Markus Grompe
The biliary system plays an important role in several acquired and genetic disorders of the liver. We have previously shown that biliary duct epithelium contains cells giving rise to proliferative Lgr5(+) organoids in vitro. However, it remained unknown whether all biliary cells or only a specific subset had this clonogenic activity. The cell surface protease ST14 was identified as a positive marker for the clonogenic subset of cholangiocytes and was used to separate clonogenic and non-clonogenic duct cells by fluorescence-activated cell sorting...
July 4, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28712848/a-short-region-of-connexin43-reduces-human-glioma-stem-cell-migration-invasion-and-survival-through-src-pten-and-fak
#4
Myriam Jaraíz-Rodríguez, Ma Dolores Tabernero, María González-Tablas, Alvaro Otero, Alberto Orfao, Jose M Medina, Arantxa Tabernero
Connexin43 (CX43), a protein that forms gap junction channels and hemichannels in astrocytes, is downregulated in high-grade gliomas. Its relevance for glioma therapy has been thoroughly explored; however, its positive effects on proliferation are counterbalanced by its effects on migration and invasion. Here, we show that a cell-penetrating peptide based on CX43 (TAT-Cx43266-283) inhibited c-Src and focal adhesion kinase (FAK) and upregulated phosphatase and tensin homolog in glioma stem cells (GSCs) derived from patients...
July 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28712847/pluri-iq-quantification-of-embryonic-stem-cell-pluripotency-through-an%C3%A2-image-based-analysis-software
#5
Tânia Perestrelo, Weitong Chen, Marcelo Correia, Christopher Le, Sandro Pereira, Ana S Rodrigues, Maria I Sousa, João Ramalho-Santos, Denis Wirtz
Image-based assays, such as alkaline phosphatase staining or immunocytochemistry for pluripotent markers, are common methods used in the stem cell field to assess pluripotency. Although an increased number of image-analysis approaches have been described, there is still a lack of software availability to automatically quantify pluripotency in large images after pluripotency staining. To address this need, we developed a robust and rapid image processing software, Pluri-IQ, which allows the automatic evaluation of pluripotency in large low-magnification images...
July 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28689997/dynamic-reorganization-of-nucleosome-positioning-in-somatic-cells-after-transfer-into-porcine-enucleated-oocytes
#6
Chenyu Tao, Juan Li, Xia Zhang, Baobao Chen, Daming Chi, Yaqiong Zeng, Yingjie Niu, Chengfei Wang, Wei Cheng, Wangjun Wu, Zengxiang Pan, Jinmin Lian, Honglin Liu, Yi-Liang Miao
The nucleosome, the fundamental structural unit of chromatin, is a critical regulator of gene expression. The mechanisms governing changes to nucleosome occupancy and positioning during somatic cell reprogramming remain poorly understood. We established a method for generating genome-wide nucleosome maps of porcine embryonic fibroblasts (PEF), reconstructed 1-cell embryos generated by somatic cell nuclear transfer (SCNT), and fertilized zygotes (FZ) using MNase sequencing with only 1,000 cells. We found that donor PEF chromatin, especially X chromosome, became more open after transfer into porcine oocytes and nucleosome occupancy decreased in promoters but increased in the genic regions...
July 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28689994/rbp4-stra6-pathway-drives-cancer-stem-cell-maintenance-and-mediates-high-fat-diet-induced-colon-carcinogenesis
#7
Sheelarani Karunanithi, Liraz Levi, Jennifer DeVecchio, George Karagkounis, Ofer Reizes, Justin D Lathia, Matthew F Kalady, Noa Noy
The transmembrane protein, STRA6, functions as a vitamin A transporter and a cytokine receptor when activated by vitamin A-bound serum retinol binding protein 4 (RBP4). STRA6 activation transduces a JAK2-STAT3 signaling cascade and promotes tumorigenesis in a xenograft mouse model of colon cancer. We show here that RBP4 and STRA6 expression is associated with poor oncologic prognosis. Downregulating STRA6 or RBP4 in colon cancer cells decreased the fraction of cancer stem cells and their sphere and tumor initiation frequency...
July 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28689993/mapt-genetic-variation-and-neuronal-maturity-alter-isoform-expression-affecting-axonal-transport-in-ipsc-derived-dopamine-neurons
#8
Joel E Beevers, Mang Ching Lai, Emma Collins, Heather D E Booth, Federico Zambon, Laura Parkkinen, Jane Vowles, Sally A Cowley, Richard Wade-Martins, Tara M Caffrey
The H1 haplotype of the microtubule-associated protein tau (MAPT) locus is genetically associated with neurodegenerative diseases, including Parkinson's disease (PD), and affects gene expression and splicing. However, the functional impact on neurons of such expression differences has yet to be fully elucidated. Here, we employ extended maturation phases during differentiation of induced pluripotent stem cells (iPSCs) into mature dopaminergic neuronal cultures to obtain cultures expressing all six adult tau protein isoforms...
July 3, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28712846/reactive-astrocytes-promote-als-like-degeneration-and-intracellular-protein-aggregation-in-human-motor-neurons-by-disrupting-autophagy-through-tgf-%C3%AE-1
#9
Pratibha Tripathi, Natalia Rodriguez-Muela, Joseph R Klim, A Sophie de Boer, Sahil Agrawal, Jackson Sandoe, Claudia S Lopes, Karolyn Sassi Ogliari, Luis A Williams, Matthew Shear, Lee L Rubin, Kevin Eggan, Qiao Zhou
Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing motor neuron disease. Astrocytic factors are known to contribute to motor neuron degeneration and death in ALS. However, the role of astrocyte in promoting motor neuron protein aggregation, a disease hallmark of ALS, remains largely unclear. Here, using culture models of human motor neurons and primary astrocytes of different genotypes (wild-type or SOD1 mutant) and reactive states (non-reactive or reactive), we show that reactive astrocytes, regardless of their genotypes, reduce motor neuron health and lead to moderate neuronal loss...
June 29, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28700896/assessing-the-safety-of-human-pluripotent-stem-cells-and-their-derivatives-for-clinical-applications
#10
Peter W Andrews, Uri Ben-David, Nissim Benvenisty, Peter Coffey, Kevin Eggan, Barbara B Knowles, Andras Nagy, Martin Pera, Benjamin Reubinoff, Peter J Rugg-Gunn, Glyn N Stacey
Pluripotent stem cells may acquire genetic and epigenetic variants during culture following their derivation. At a conference organized by the International Stem Cell Initiative, and held at The Jackson Laboratory, Bar Harbor, Maine, October 2016, participants discussed how the appearance of such variants can be monitored and minimized and, crucially, how their significance for the safety of therapeutic applications of these cells can be assessed. A strong recommendation from the meeting was that an international advisory group should be set up to review the genetic and epigenetic changes observed in human pluripotent stem cell lines and establish a framework for evaluating the risks that they may pose for clinical use...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28669604/redox-homeostasis-plays-important-roles-in-the-maintenance-of-the-drosophila-testis-germline-stem-cells
#11
Sharon Wui Sing Tan, Qian Ying Lee, Belinda Shu Ee Wong, Yu Cai, Gyeong Hun Baeg
Oxidative stress influences stem cell behavior by promoting the differentiation, proliferation, or apoptosis of stem cells. Thus, characterizing the effects of reactive oxygen species (ROS) on stem cell behavior provides insights into the significance of redox homeostasis in stem cell-associated diseases and efficient stem cell expansion for cellular therapies. We utilized the Drosophila testis as an in vivo model to examine the effects of ROS on germline stem cell (GSC) maintenance. High levels of ROS induced by alteration in Keap1/Nrf2 activity decreased GSC number by promoting precocious GSC differentiation...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28669603/nodal-secures-pluripotency-upon-embryonic-stem-cell-progression-from%C3%A2-the-ground-state
#12
Carla Mulas, Tüzer Kalkan, Austin Smith
Naive mouse embryonic stem cells (ESCs) can develop multiple fates, but the cellular and molecular processes that enable lineage competence are poorly characterized. Here, we investigated progression from the ESC ground state in defined culture. We utilized downregulation of Rex1::GFPd2 to track the loss of ESC identity. We found that cells that have newly downregulated this reporter have acquired capacity for germline induction. They can also be efficiently specified for different somatic lineages, responding more rapidly than naive cells to inductive cues...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28669602/the-bile-acid-nuclear-receptor-fxr%C3%AE-is-a-critical-regulator-of-mouse-germ-cell-fate
#13
Emmanuelle Martinot, Lauriane Sèdes, Marine Baptissart, Hélène Holota, Betty Rouaisnel, Christelle Damon-Soubeyrand, Angélique De Haze, Jean-Paul Saru, Christelle Thibault-Carpentier, Céline Keime, Jean-Marc A Lobaccaro, Silvère Baron, Gérard Benoit, Françoise Caira, Claude Beaudoin, David H Volle
Spermatogenesis is the process by which spermatozoa are generated from spermatogonia. This cell population is heterogeneous, with self-renewing spermatogonial stem cells (SSCs) and progenitor spermatogonia that will continue on a path of differentiation. Only SSCs have the ability to regenerate and sustain spermatogenesis. This makes the testis a good model to investigate stem cell biology. The Farnesoid X Receptor alpha (FXRα) was recently shown to be expressed in the testis. However, its global impact on germ cell homeostasis has not yet been studied...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28669601/electrical-guidance-of-human-stem-cells-in-the-rat-brain
#14
Jun-Feng Feng, Jing Liu, Lei Zhang, Ji-Yao Jiang, Michael Russell, Bruce G Lyeth, Jan A Nolta, Min Zhao
Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28669600/bace1-deficiency-causes-abnormal-neuronal-clustering-in-the-dentate-gyrus
#15
Hailong Hou, Qingyuan Fan, Wanxia He, Hoonkyo Suh, Xiangyou Hu, Riqiang Yan
BACE1 is validated as Alzheimer's β-secretase and a therapeutic target for Alzheimer's disease. In examining BACE1-null mice, we discovered that BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone (SPZ). Such clusters were rarely observed in wild-type SPZ and not reported in other mouse models. To understand their origins and fates, we examined how neuroblasts in BACE1-null SPZ mature and migrate during early postnatal development...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28669599/inactivation-of-stat3-signaling-impairs-hair-cell-differentiation-in%C3%A2-the%C3%A2-developing-mouse-cochlea
#16
Qianqian Chen, Yizhou Quan, Naitao Wang, Chengying Xie, Zhongzhong Ji, Hao He, Renjie Chai, Huawei Li, Shankai Yin, Y Eugene Chin, Xunbin Wei, Wei-Qiang Gao
Although STAT3 signaling is demonstrated to regulate sensory cell differentiation and regeneration in the zebrafish, its exact role is still unclear in mammalian cochleae. Here, we report that STAT3 and its activated form are specifically expressed in hair cells during mouse cochlear development. Importantly, conditional cochlear deletion of Stat3 leads to an inhibition on hair cell differentiation in mice in vivo and in vitro. By cell fate analysis, inactivation of STAT3 signaling shifts the cell division modes from asymmetric to symmetric divisions from supporting cells...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28648900/tet-catalyzed-5-hydroxymethylation-precedes-hnf4a-promoter-choice-during-differentiation-of-bipotent-liver-progenitors
#17
Pierre-Benoit Ancey, Szilvia Ecsedi, Marie-Pierre Lambert, Fazlur Rahman Talukdar, Marie-Pierre Cros, Denise Glaise, Diana Maria Narvaez, Veronique Chauvet, Zdenko Herceg, Anne Corlu, Hector Hernandez-Vargas
Understanding the processes that govern liver progenitor cell differentiation has important implications for the design of strategies targeting chronic liver diseases, whereby regeneration of liver tissue is critical. Although DNA methylation (5mC) and hydroxymethylation (5hmC) are highly dynamic during early embryonic development, less is known about their roles at later stages of differentiation. Using an in vitro model of hepatocyte differentiation, we show here that 5hmC precedes the expression of promoter 1 (P1)-dependent isoforms of HNF4A, a master transcription factor of hepatocyte identity...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28648899/transient-hes5-activity-instructs-mesodermal-cells-toward-a-cardiac-fate
#18
Ana G Freire, Avinash Waghray, Francisca Soares-da-Silva, Tatiana P Resende, Dung-Fang Lee, Carlos-Filipe Pereira, Diana S Nascimento, Ihor R Lemischka, Perpétua Pinto-do-Ó
Notch signaling plays a role in specifying a cardiac fate but the downstream effectors remain unknown. In this study we implicate the Notch downstream effector HES5 in cardiogenesis. We show transient Hes5 expression in early mesoderm of gastrulating embryos and demonstrate, by loss and gain-of-function experiments in mouse embryonic stem cells, that HES5 favors cardiac over primitive erythroid fate. Hes5 overexpression promotes upregulation of the cardiac gene Isl1, while the hematopoietic regulator Scl is downregulated...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28648898/genome-wide-single-cell-dna-methylomics-reveals-increased-non-cpg-methylation-during-human-oocyte-maturation
#19
Bo Yu, Xiao Dong, Silvia Gravina, Önder Kartal, Timothy Schimmel, Jacques Cohen, Drew Tortoriello, Raifa Zody, R David Hawkins, Jan Vijg
The establishment of DNA methylation patterns in oocytes is a highly dynamic process marking gene-regulatory events during fertilization, embryonic development, and adulthood. However, after epigenetic reprogramming in primordial germ cells, how and when DNA methylation is re-established in developing human oocytes remains to be characterized. Here, using single-cell whole-genome bisulfite sequencing, we describe DNA methylation patterns in three different maturation stages of human oocytes. We found that while broad-scale patterns of CpG methylation have been largely established by the immature germinal vesicle stage, localized changes continue into later development...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28648897/unique-organization-of-the-nuclear-envelope-in-the-post-natal-quiescent-neural-stem-cells
#20
Arantxa Cebrián-Silla, Clara Alfaro-Cervelló, Vicente Herranz-Pérez, Naoko Kaneko, Dae Hwi Park, Kazunobu Sawamoto, Arturo Alvarez-Buylla, Daniel A Lim, José Manuel García-Verdugo
Neural stem cells (B1 astrocytes; NSCs) in the adult ventricular-subventricular-zone (V-SVZ) originate in the embryo. Surprisingly, recent work has shown that B1 cells remain largely quiescent. They are reactivated postnatally to function as primary progenitors for neurons destined for the olfactory bulb and some corpus callosum oligodendrocytes. The cellular and molecular properties of quiescent B1 cells remain unknown. Here we found that a subpopulation of B1 cells has a unique nuclear envelope invagination specialization similar to envelope-limited chromatin sheets (ELCS), reported in certain lymphocytes and some cancer cells...
July 11, 2017: Stem Cell Reports
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