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Stem Cell Reports

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https://www.readbyqxmd.com/read/28089669/exposure-to-gdnf-enhances-the-ability-of-enteric-neural-progenitors-to%C3%A2-generate-an-enteric-nervous-system
#1
Sonja J McKeown, Mitra Mohsenipour, Annette J Bergner, Heather M Young, Lincon A Stamp
Cell therapy is a promising approach to generate an enteric nervous system (ENS) and treat enteric neuropathies. However, for translation to the clinic, it is highly likely that enteric neural progenitors will require manipulation prior to transplantation to enhance their ability to migrate and generate an ENS. In this study, we examine the effects of exposure to several factors on the ability of ENS progenitors, grown as enteric neurospheres, to migrate and generate an ENS. Exposure to glial-cell-line-derived neurotrophic factor (GDNF) resulted in a 14-fold increase in neurosphere volume and a 12-fold increase in cell number...
January 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28089671/pdgfr%C3%AE-cells-in-embryonic-stem-cell-cultures-represent-the-in%C3%A2-vitro-equivalent-of-the-pre-implantation-primitive-endoderm-precursors
#2
Antonio Lo Nigro, Anchel de Jaime-Soguero, Rita Khoueiry, Dong Seong Cho, Giorgia Maria Ferlazzo, Ilaria Perini, Vanesa Abon Escalona, Xabier Lopez Aranguren, Susana M Chuva de Sousa Lopes, Kian Peng Koh, Pier Giulio Conaldi, Wei-Shou Hu, An Zwijsen, Frederic Lluis, Catherine M Verfaillie
In early mouse pre-implantation development, primitive endoderm (PrE) precursors are platelet-derived growth factor receptor alpha (PDGFRα) positive. Here, we demonstrated that cultured mouse embryonic stem cells (mESCs) express PDGFRα heterogeneously, fluctuating between a PDGFRα+ (PrE-primed) and a platelet endothelial cell adhesion molecule 1 (PECAM1)-positive state (epiblast-primed). The two surface markers can be co-detected on a third subpopulation, expressing epiblast and PrE determinants (double-positive)...
January 5, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28089670/in%C3%A2-vitro-propagation-and-branching-morphogenesis-from-single-ureteric-bud%C3%A2-cells
#3
Shunsuke Yuri, Masaki Nishikawa, Naomi Yanagawa, Oak D Jo, Norimoto Yanagawa
A method to maintain and rebuild ureteric bud (UB)-like structures from UB cells in vitro could provide a useful tool for kidney regeneration. We aimed in our present study to establish a serum-free culture system that enables the expansion of UB progenitor cells, i.e., UB tip cells, and reconstruction of UB-like structures. We found that fibroblast growth factors or retinoic acid (RA) was sufficient for the survival of UB cells in serum-free condition, while the proliferation and maintenance of UB tip cells required glial cell-derived neurotrophic factor together with signaling from either WNT-β-catenin pathway or RA...
January 5, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28089668/ebio-does-not-induce-cardiomyogenesis-in-human-pluripotent-stem-cells-but-modulates-cardiac-subtype-enrichment-by-lineage-selective-survival
#4
Monica Jara-Avaca, Henning Kempf, Michael Rückert, Diana Robles-Diaz, Annika Franke, Jeanne de la Roche, Martin Fischer, Daniela Malan, Philipp Sasse, Wladimir Solodenko, Gerald Dräger, Andreas Kirschning, Ulrich Martin, Robert Zweigerdt
Subtype-specific human cardiomyocytes (CMs) are valuable for basic and applied research. Induction of cardiomyogenesis and enrichment of nodal-like CMs was described for mouse pluripotent stem cells (mPSCs) in response to 1-ethyl-2-benzimidazolinone (EBIO), a chemical modulator of small-/intermediate-conductance Ca(2+)-activated potassium channels (SKs 1-4). Investigating EBIO in human pluripotent stem cells (PSCs), we have applied three independent differentiation protocols of low to high cardiomyogenic efficiency...
January 4, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28065643/ctip-specific-roles-during-cell-reprogramming-have-long-term-consequences-in-the-survival-and-fitness-of-induced-pluripotent-stem-cells
#5
Daniel Gómez-Cabello, Cintia Checa-Rodríguez, María Abad, Manuel Serrano, Pablo Huertas
Acquired genomic instability is one of the major concerns for the clinical use of induced pluripotent stem cells (iPSCs). All reprogramming methods are accompanied by the induction of DNA damage, of which double-strand breaks are the most cytotoxic and mutagenic. Consequently, DNA repair genes seem to be relevant for accurate reprogramming to minimize the impact of such DNA damage. Here, we reveal that reprogramming is associated with high levels of DNA end resection, a critical step in homologous recombination...
December 27, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/28065642/mesenchymal-to-epithelial-transition-mediated-by-cdh1-promotes-spontaneous-reprogramming-of-male-germline-stem-cells-to-pluripotency
#6
Junhui An, Yu Zheng, Christina Tenenhaus Dann
Cultured spermatogonial stem cells (GSCs) can spontaneously form pluripotent cells in certain culture conditions. However, GSC reprogramming is a rare event that is largely unexplained. We show GSCs have high expression of mesenchymal to epithelial transition (MET) suppressors resulting in a developmental barrier inhibiting GSC reprogramming. Either increasing OCT4 or repressing transforming growth factor β (TGF-β) signaling promotes GSC reprogramming by upregulating CDH1 and boosting MET. Reducing ZEB1 also enhances GSC reprogramming through its direct effect on CDH1...
December 24, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/28065644/in%C3%A2-vivo-maturation-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-in-neonatal-and-adult-rat-hearts
#7
Shin Kadota, Lil Pabon, Hans Reinecke, Charles E Murry
We hypothesized that the neonatal rat heart would bring transplanted human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to maturity as it grows to adult size. In neonatal rat heart, engrafted hiPSC derivatives developed partially matured myofibrils after 3 months, with increasing cell size and sarcomere length. There was no difference between grafts from hiPSC-CMs or hiPSC-derived cardiac progenitors (hiPSC-CPs) at 3 months, nor was maturation influenced by infarction. Interestingly, the infarcted adult heart induced greater human cardiomyocyte hypertrophy and induction of cardiac troponin I expression than the neonatal heart...
November 22, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/28076758/polysaccharides-from-ganoderma-lucidum-promote-cognitive-function-and%C3%A2-neural-progenitor-proliferation-in-mouse-model-of-alzheimer-s-disease
#8
Shichao Huang, Jianxin Mao, Kan Ding, Yue Zhou, Xianglu Zeng, Wenjuan Yang, Peipei Wang, Cun Zhao, Jian Yao, Peng Xia, Gang Pei
Promoting neurogenesis is a promising strategy for the treatment of cognition impairment associated with Alzheimer's disease (AD). Ganoderma lucidum is a revered medicinal mushroom for health-promoting benefits in the Orient. Here, we found that oral administration of the polysaccharides and water extract from G. lucidum promoted neural progenitor cell (NPC) proliferation to enhance neurogenesis and alleviated cognitive deficits in transgenic AD mice. G. lucidum polysaccharides (GLP) also promoted self-renewal of NPC in cell culture...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28076757/ipsc-derived-retina-transplants-improve-vision-in-rd1-end-stage-retinal-degeneration-mice
#9
Michiko Mandai, Momo Fujii, Tomoyo Hashiguchi, Genshiro A Sunagawa, Shinichiro Ito, Jianan Sun, Jun Kaneko, Junki Sho, Chikako Yamada, Masayo Takahashi
Recent success in functional recovery by photoreceptor precursor transplantation in dysfunctional retina has led to an increased interest in using embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal progenitors to treat retinal degeneration. However, cell-based therapies for end-stage degenerative retinas that have lost the outer nuclear layer (ONL) are still a big challenge. In the present study, by transplanting mouse iPSC-derived retinal tissue (miPSC retina) in the end-stage retinal-degeneration model (rd1), we visualized the direct contact between host bipolar cell terminals and the presynaptic terminal of graft photoreceptors by gene labeling, showed light-responsive behaviors in transplanted rd1 mice, and recorded responses from the host retina with transplants by ex vivo micro-electroretinography and ganglion cell recordings using a multiple-electrode array system...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28076756/dissociation-of-survival-proliferation-and-state-control-in-human-hematopoietic-stem-cells
#10
David J H F Knapp, Colin A Hammond, Paul H Miller, Gabrielle M Rabu, Philip A Beer, Marketa Ricicova, Véronique Lecault, Daniel Da Costa, Michael VanInsberghe, Alice M Cheung, Davide Pellacani, James Piret, Carl Hansen, Connie J Eaves
The role of growth factors (GFs) in controlling the biology of human hematopoietic stem cells (HSCs) remains limited by a lack of information concerning the individual and combined effects of GFs directly on the survival, Mitogenesis, and regenerative activity of highly purified human HSCs. We show that the initial input HSC activity of such a purified starting population of human cord blood cells can be fully maintained over a 21-day period in serum-free medium containing five GFs alone. HSC survival was partially supported by any one of these GFs, but none were essential, and different combinations of GFs variably stimulated HSC proliferation...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28076755/rad51-is-a-selective-dna-repair-target-to-radiosensitize-glioma-stem-cells
#11
Harry O King, Tim Brend, Helen L Payne, Alexander Wright, Thomas A Ward, Karan Patel, Teklu Egnuni, Lucy F Stead, Anjana Patel, Heiko Wurdak, Susan C Short
Patients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair protein RAD51 is highly expressed in GSCs, which are reliant on RAD51-dependent DSB repair after radiation. RAD51 expression and RAD51 foci numbers fall when these cells move toward astrocytic differentiation...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28041879/mapping-whole-transcriptome-splicing-in-mouse-hematopoietic-stem-cells
#12
Oron Goldstein, Karin Meyer, Yariv Greenshpan, Nir Bujanover, Mili Feigin, Hadas Ner-Gaon, Tal Shay, Roi Gazit
Hematopoietic stem cells (HSCs) are rare cells that generate all the various types of blood and immune cells. High-quality transcriptome data have enabled the identification of significant genes for HSCs. However, most genes are expressed in various forms by alternative splicing (AS), extending transcriptome complexity. Here, we delineate AS to determine which isoforms are expressed in mouse HSCs. Our analysis of microarray and RNA-sequencing data includes differential expression of splicing factors that may regulate AS, and a complete map of splicing isoforms...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28041878/epigenetic-modifiers-facilitate-induction-and-pluripotency-of-porcine-ipscs
#13
Jian Mao, Qian Zhang, Wei Deng, Hua Wang, Kai Liu, Haifeng Fu, Qiang Zhao, Xumin Wang, Lin Liu
Inadequate silencing of exogenous genes represents a major obstacle to complete epigenetic reprogramming of porcine-induced pluripotent stem cells (piPSCs) by conventional pluripotency transcription factors (OSKM). We tested the hypothesis that epigenetic modification by active DNA or histone demethylation or by inhibition of histone deacetylase would enhance reprogramming and exogenous gene silencing in piPSCs. piPSCs induced by OSKM in combination with epigenetic factors, specifically Ten-Eleven Translocation (Tet1 or Tet3) or lysine (K)-specific demethylase 3A (Kdm3a), expressed higher levels of Rex1 and other genes representing naive state and exhibited more open chromatin status, compared with those of OSKM controls...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28041877/cytosine-5-rna-methylation-regulates-neural-stem-cell-differentiation-and%C3%A2-motility
#14
Joana V Flores, Lucía Cordero-Espinoza, Feride Oeztuerk-Winder, Amanda Andersson-Rolf, Tommaso Selmi, Sandra Blanco, Jignesh Tailor, Sabine Dietmann, Michaela Frye
Loss-of-function mutations in the cytosine-5 RNA methylase NSUN2 cause neurodevelopmental disorders in humans, yet the underlying cellular processes leading to the symptoms that include microcephaly remain unclear. Here, we show that NSUN2 is expressed in early neuroepithelial progenitors of the developing human brain, and its expression is gradually reduced during differentiation of human neuroepithelial stem (NES) cells in vitro. In the developing Nsun2(-/-) mouse cerebral cortex, intermediate progenitors accumulate and upper-layer neurons decrease...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28041876/a-functional-bioluminescent-zebrafish-screen-for-enhancing-hematopoietic-cell-homing
#15
Yuliana Astuti, Ashley C Kramer, Amanda L Blake, Bruce R Blazar, Jakub Tolar, Mandy E Taisto, Troy C Lund
To discover small molecules that modulate hematopoietic cell homing after adoptive transfer, we created a transgenic zebrafish expressing firefly luciferase downstream of the ubiquitin promoter (ubi:luc) to serve as a hematopoietic donor. Bioluminescence imaging (BLI) was used to detect and follow ubi:luc hematopoietic cells that homed to the marrow as early as 1 day post-transplant. BLI was able to detect the biological effect of prostaglandin E2 on early homing/engraftment of donor hematopoietic cells. This system was utilized in a functional screen of small molecules to enhance homing/engraftment...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28041875/snev-hprp19-hpso4-regulates-adipogenesis-of-human-adipose-stromal-cells
#16
Abdulhameed Khan, Hanna Dellago, Lucia Terlecki-Zaniewicz, Michael Karbiener, Sylvia Weilner, Florian Hildner, Viktoria Steininger, Christian Gabriel, Christoph Mück, Pidder Jansen-Dürr, Ara Hacobian, Marcel Scheideler, Regina Grillari-Voglauer, Markus Schosserer, Johannes Grillari
Aging is accompanied by loss of subcutaneous adipose tissue. This may be due to reduced differentiation capacity or deficiency in DNA damage repair (DDR) factors. Here we investigated the role of SNEV(hPrp19/hPso4), which was implicated in DDR and senescence evasion, in adipogenic differentiation of human adipose stromal cells (hASCs). We showed that SNEV is induced during adipogenesis and localized both in the nucleus and in the cytoplasm. Knockdown of SNEV perturbed adipogenic differentiation and led to accumulation of DNA damage in hASCs upon oxidative stress...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28017658/vitamin-c-and-l-proline-antagonistic-effects-capture-alternative-states-in-the-pluripotency-continuum
#17
Cristina D'Aniello, Ehsan Habibi, Federica Cermola, Debora Paris, Francesco Russo, Alessandro Fiorenzano, Gabriele Di Napoli, Dominique J Melck, Gilda Cobellis, Claudia Angelini, Annalisa Fico, Robert Blelloch, Andrea Motta, Hendrik G Stunnenberg, Dario De Cesare, Eduardo J Patriarca, Gabriella Minchiotti
Metabolites and cofactors are emerging as key regulators of cell plasticity and reprogramming, and their role in the control of pluripotency is just being discovered. Here we provide unprecedented evidence that embryonic stem cell (ESC) pluripotency relies on the relative levels of two physiological metabolites, namely ascorbic acid (vitamin C, VitC) and l-proline (l-Pro), which affect global DNA methylation, transcriptional profile, and energy metabolism. Specifically, while a high VitC/l-Pro ratio drives ESCs toward a naive state, the opposite condition (l-Pro excess) captures a fully reversible early primed pluripotent state, which depends on autocrine fibroblast growth factor and transforming growth factor β signaling pathways...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28017657/direct-reprogramming-of-mouse-fibroblasts-toward-leydig-like-cells-by-defined-factors
#18
Yan Yang, Ziyi Li, Xupeng Wu, Haolin Chen, Wenting Xu, Qi Xiang, Qihao Zhang, Jie Chen, Ren-Shan Ge, Zhijian Su, Yadong Huang
Leydig cells (LCs) play crucial roles in producing testosterone, and their dysfunction leads to male hypogonadism. LC transplantation is a promising alternative therapy for male hypogonadism. However, the source of LCs limits this strategy for clinical applications. Here, we report our success in reprogramming mice fibroblasts into LCs by expressing three transcriptional factors, Dmrt1, Gata4, and Nr5a1. The induced Leydig-like cells (iLCs) expressed steroidogenic genes, had a global gene expression profile similar to that of adult LCs, and acquired androgen synthesis capabilities...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28017656/primary-human-testicular-cells-self-organize-into-organoids-with-testicular-properties
#19
Yoni Baert, Joery De Kock, João P Alves-Lopes, Olle Söder, Jan-Bernd Stukenborg, Ellen Goossens
So far, successful de novo formation of testicular tissue followed by complete spermatogenesis in vitro has been achieved only in rodents. Our findings reveal that primary human testicular cells are able to self-organize into human testicular organoids (TOs), i.e., multi-cellular tissue surrogates, either with or without support of a biological scaffold. Despite lacking testis-specific topography, these mini-tissues harbored spermatogonia and their important niche cells, which retained specific functionalities during long-term culture...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28017655/cd59-regulation-by-sox2-is-required-for-epithelial-cancer-stem-cells-to-evade-complement-surveillance
#20
Jianfeng Chen, Peipei Ding, Ling Li, Hongyu Gu, Xin Zhang, Long Zhang, Na Wang, Lu Gan, Qi Wang, Wei Zhang, Weiguo Hu
Cancer stem cells (CSCs) are highly associated with therapy resistance and metastasis. Interplay between CSCs and various immune components is required for tumor survival. However, the response of CSCs to complement surveillance remains unknown. Herein, using stem-like sphere-forming cells prepared from a mammary tumor and a lung adenocarcinoma cell line, we found that CD59 was upregulated to protect CSCs from complement-dependent cytotoxicity. CD59 silencing significantly enhanced complement destruction and completely suppressed tumorigenesis in CSC-xenografted nude mice...
January 10, 2017: Stem Cell Reports
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