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Stem Cell Research

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https://www.readbyqxmd.com/read/28941410/the-contribution-of-human-non-human-animal-chimeras-to-stem-cell-research
#1
REVIEW
Sonya Levine, Laura Grabel
Chimeric animals are made up of cells from two separate zygotes. Human/non-human animal chimeras have been used for a number of research purposes, including human disease modeling. Pluripotent stem cell (PSC) research has relied upon the chimera approach to examine the developmental potential of stem cells, to determine the efficacy of cell replacement therapies, and to establish a means of producing human organs. Based on ethical issues, this work has faced pushback from various sources including funding agencies...
September 14, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28926760/laminin-%C3%AE-5-substrates-promote-survival-network-formation-and-functional-development-of-human-pluripotent-stem-cell-derived-neurons-in-vitro
#2
Anu Hyysalo, Mervi Ristola, Meeri E-L Mäkinen, Sergei Häyrynen, Matti Nykter, Susanna Narkilahti
Laminins are one of the major protein groups in the extracellular matrix (ECM) and specific laminin isoforms are crucial for neuronal functions in the central nervous system in vivo. In the present study, we compared recombinant human laminin isoforms (LN211, LN332, LN411, LN511, and LN521) and laminin isoform fragment (LN511-E8) in in vitro cultures of human pluripotent stem cell (hPSC)-derived neurons. We showed that laminin substrates containing the α5-chain are important for neuronal attachment, viability and network formation, as detected by phase contrast imaging, viability staining, and immunocytochemistry...
September 12, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28889080/reprogramming-of-rabbit-induced-pluripotent-stem-cells-toward-epiblast-and-chimeric-competency-using-kr%C3%A3-ppel-like-factors
#3
Yann Tapponnier, Marielle Afanassieff, Irène Aksoy, Maxime Aubry, Anaïs Moulin, Lucas Medjani, Wilhelm Bouchereau, Chloé Mayère, Pierre Osteil, Jazmine Nurse-Francis, Ioannis Oikonomakos, Thierry Joly, Luc Jouneau, Catherine Archilla, Barbara Schmaltz-Panneau, Nathalie Peynot, Harmonie Barasc, Alain Pinton, Jérome Lecardonnel, Elen Gocza, Nathalie Beaujean, Véronique Duranthon, Pierre Savatier
Rabbit induced pluripotent stem cells (rbiPSCs) possess the characteristic features of primed pluripotency as defined in rodents and primates. In the present study, we reprogrammed rbiPSCs using human Krüppel-like factors (KLFs) 2 and 4 and cultured them in a medium supplemented with fetal calf serum and leukemia inhibitory factor. These cells (designated rbEKA) were propagated by enzymatic dissociation for at least 30 passages, during which they maintained a normal karyotype. This new culturing protocol resulted in transcriptional and epigenetic reconfiguration, as substantiated by the expression of transcription factors and the presence of histone modifications associated with naïve pluripotency...
September 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28886418/chemically-induced-photoreceptor-degeneration-and-protection-in-mouse-ipsc-derived-three-dimensional-retinal-organoids
#4
Shin-Ichiro Ito, Akishi Onishi, Masayo Takahashi
Induced pluripotent stem cells (iPSCs), which can be differentiated into various tissues and cell types, have been used for clinical research and disease modeling. Self-organizing three-dimensional (3D) tissue engineering has been established within the past decade and enables researchers to obtain tissues and cells that almost mimic in vivo development. However, there are no reports of practical experimental procedures that reproduce photoreceptor degeneration. In this study, we induced photoreceptor cell death in mouse iPSC-derived 3D retinal organoids (3D-retinas) by 4-hydroxytamoxifen (4-OHT), which induces photoreceptor degeneration in mouse retinal explants, and then established a live-cell imaging system to measure degeneration-related properties...
August 24, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28843157/epidermal-growth-factor-as-a-mechanosensitizer-in-human-bone-marrow-stromal-cells
#5
Sigrid Müller-Deubert, Lothar Seefried, Melanie Krug, Franz Jakob, Regina Ebert
Epidermal growth factors (EGFs) e.g. EGF, heparin-binding EGF and transforming growth factor alpha and their receptors e.g. EGFR and ErbB2 control proinflammatory signaling and modulate proliferation in bone marrow stromal cells (BMSC). Interleukin-6 and interleukin-8 are EGF targets and participate in the inflammatory phase of bone regeneration via non-canonical wnt signaling. BMSC differentiation is also influenced by mechanical strain-related activation of ERK1/2 and AP-1, but the role of EGFR signaling in mechanotransduction is unclear...
August 18, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28826027/crispr-cas9-and-piggybac-mediated-footprint-free-lrrk2-g2019s-knock-in-reveals-neuronal-complexity-phenotypes-and-%C3%AE-synuclein-modulation-in-dopaminergic-neurons
#6
Xiaobing Qing, Jonas Walter, Javier Jarazo, Jonathan Arias-Fuenzalida, Anna-Lena Hillje, Jens C Schwamborn
The p.G2019S mutation of the leucine-rich repeat kinase 2 (LRRK2) has been identified as the most prevalent genetic cause of familial and sporadic Parkinson's disease (PD). The Cre-LoxP recombination system has been used to correct the LRRK2-G2019S mutation in patient derived human induced pluripotent stem cells (hiPSCs) in order to generate isogenic controls. However, the remaining LoxP site can influence gene expression. In this study, we report the generation of a footprint-free LRRK2-G2019S isogenic hiPS cell line edited with the CRISPR/Cas9 and piggyBac technologies...
August 18, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28843156/small-molecule-at7867-proliferates-pdx1-expressing-pancreatic-progenitor-cells-derived-from-human-pluripotent-stem-cells
#7
Azuma Kimura, Taro Toyoda, Yohei Nishi, Makoto Nasu, Akira Ohta, Kenji Osafune
While pancreatic islet transplantation achieves insulin independence in type 1 diabetes (T1D) patients, its widespread application is limited by donor tissue scarcity. Pancreatic progenitor cells (PPCs) give rise to all cell types in the pancreas during development. PPCs derived from human pluripotent stem cells have been shown to differentiate into functional β cells both in vitro and in vivo, and to reverse hyperglycemia, at least in mice. Therefore, PPCs have great potential to serve as an alternative cell source for cell therapy, and the identification of compounds that facilitate PPC proliferation could provide stable and large-scale pancreatic cell preparation systems in clinical settings...
August 17, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28841424/mechanical-induction-of-dentin-like-differentiation-by-adult-mouse-bone-marrow-stromal-cells-using-compressive-scaffolds
#8
Basma Hashmi, Tadanori Mammoto, James Weaver, Thomas Ferrante, Amanda Jiang, Elisabeth Jiang, Juani Feliz, Donald E Ingber
Tooth formation during embryogenesis is controlled through a complex interplay between mechanical and chemical cues. We have previously shown that physical cell compaction of dental mesenchyme cells during mesenchymal condensation is responsible for triggering odontogenic differentiation during embryogenesis, and that expression of Collagen VI stabilizes this induction. In addition, we have shown that synthetic polymer scaffolds that artificially induce cell compaction can induce embryonic mandible mesenchymal cells to initiate tooth differentiation both in vitro and in vivo...
August 17, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28774758/dmrt-proteins-and-coordination-of-mammalian-spermatogenesis
#9
Teng Zhang, David Zarkower
DMRT genes encode a deeply conserved family of transcription factors that share a unique DNA binding motif, the DM domain. DMRTs regulate development in a broad variety of metazoans and they appear to have controlled sexual differentiation for hundreds of millions of years. In mice, starting during embryonic development, three Dmrt genes act sequentially to help establish and maintain spermatogenesis. Dmrt1 has notably diverse functions that include repressing pluripotency genes and promoting mitotic arrest in embryonic germ cells, reactivating prospermatogonia perinatally, establishing and maintaining spermatogonial stem cells (SSCs), promoting spermatogonial differentiation, and controlling the mitosis/meiosis switch...
July 25, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28801028/convergent-evolution-of-germ-granule-nucleators-a-hypothesis
#10
Arpita Kulkarni, Cassandra G Extavour
Germ cells have been considered "the ultimate stem cell" because they alone, during normal development of sexually reproducing organisms, are able to give rise to all organismal cell types. Morphological descriptions of a specialized cytoplasm termed 'germ plasm' and associated electron dense ribonucleoprotein (RNP) structures called 'germ granules' within germ cells date back as early as the 1800s. Both germ plasm and germ granules are implicated in germ line specification across metazoans. However, at a molecular level, little is currently understood about the molecular mechanisms that assemble these entities in germ cells...
July 19, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28754604/regulation-of-fetal-male-germ-cell-development-by-members-of-the-tgf%C3%AE-superfamily
#11
Cassy Spiller, Guillaume Burnet, Josephine Bowles
There is now substantial evidence that members of the transforming growth factor-β (TGFβ family) regulate germ cell development in the mouse fetal testis. Correct development of germ cells during fetal life is critical for establishment of effective spermatogenesis and for avoiding the formation of testicular germ cell cancer in later life. Here we consider the evidence for involvement of various TGFβ family members, attempt to reconcile discrepancies and clarify what we believe to be the likely in vivo roles of these factors...
July 19, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28754603/a-pilgrim-s-progress-seeking-meaning-in-primordial-germ-cell-migration
#12
Andrea V Cantú, Diana J Laird
Comparative studies of primordial germ cell (PGC) development across organisms in many phyla reveal surprising diversity in the route of migration, timing and underlying molecular mechanisms, suggesting that the process of migration itself is conserved. However, beyond the perfunctory transport of cellular precursors to their later arising home of the gonads, does PGC migration serve a function? Here we propose that the process of migration plays an additional role in quality control, by eliminating PGCs incapable of completing migration as well as through mechanisms that favor PGCs capable of responding appropriately to migration cues...
July 18, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925369/generation-of-a-gene-corrected-isogenic-control-ipsc-line-from-cystic-fibrosis-patient-specific-ipscs-homozygous-for-p-phe508del-mutation-mediated-by-talens-and-ssodn
#13
Sylvia Merkert, Christien Bednarski, Gudrun Göhring, Toni Cathomen, Ulrich Martin
Cystic fibrosis (CF) is a monogenetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which affects multiple organs. Human induced pluripotent stem cells (iPSCs) derived from CF patients and the generation of isogeneic gene-corrected control cell lines enable disease modelling, drug discovery or toxicological studies and therefore the development of CF patient-specific therapies. We have previously generated a hiPSC line from a CF patient homozygous for the p...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925368/a-marfan-syndrome-human-induced-pluripotent-stem-cell-line-with-a-heterozygous-fbn1-c-4082g-a-mutation-ismmsi002-b-for-disease-modeling
#14
Sandra Klein, Jill L Dvornik, Akshitha R Yarrabothula, Christoph Schaniel
Fibroblasts of a 28-year-old female with Marfan syndrome (MFS) due to a heterozygous FBN1 c.4082G>A mutation were reprogrammed using the Sendai virus delivery method. The established human induced pluripotent stem cell (hiPSC) line named ISMMSi002-B expresses pluripotency markers, has a normal karyotype, carries the specific FBN1 mutation and is able to differentiate into three germ layers in vitro. ISMMSi002-B has utility in studying MFS pathogenesis, including skeletal abnormalities, cardiomyopathy, and vascular smooth muscle cell dysfunction associated with aortic aneurysm...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925367/generation-of-integration-free-induced-pluripotent-stem-cells-gzhmui001-a-by-reprogramming-peripheral-blood-mononuclear-cells-from-a-47-xxx-syndrome-patient
#15
Yuchang Chen, Zhanhui Ou, Bing Song, Yexing Xian, Shuming Ouyang, Yuhuan Xie, Yanting Xue, Xiaofang Sun
47, XXX syndrome is one of several sex-chromosomal aneuploidies, and it has an incidence of approximately 1/1000 in newborn females. Because of heterogeneity in X-inactivation, these patients may exhibit a variety of clinical symptoms. Here, we report the generation of an integration-free human induced pluripotent stem cell line (GZHMUi001-A) by using Sendai virus to reprogram peripheral blood mononuclear cells from a 47, XXX syndrome patient with premature ovarian failure. This 47, XXX iPS cell line has characteristics of pluripotent stem cells and is a useful tool for the investigation of this X chromosome aneuploid disease...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925366/establishment-of-a-human-ipsc-line-iishdoi001-a-from-a-patient-with-mcardle-disease
#16
María Del Carmen Ortuño-Costela, Nathalie Rodríguez-Mancera, Marta García-López, Francisco Zurita-Díaz, Ana Moreno-Izquierdo, Alejandro Lucía, Miguel Ángel Martín, Rafael Garesse, M Esther Gallardo
Human iPSC line IISHDOi001-A was generated from fibroblasts of a patient with McArdle disease harbouring the mutation, c.148C>T; p.Arg50Ter, in the PYGM gene. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using Sendai virus.
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925365/generation-of-an-induced-pluripotent-stem-cell-ipsc-line-from-a-patient-with-maturity-onset-diabetes-of-the-young-type-13-mody13-with-a-the-potassium-inwardly-rectifying-channel-subfamily-j-member-11-kcnj11-mutation
#17
Frank Griscelli, Olivier Feraud, Tony Ernault, Noufissa Oudrihri, Ali G Turhan, Amélie Bonnefond, Philippe Froguel, Annelise Bennaceur-Griscelli
Heterozygous activating mutation (p.Glu227Lys) in KCNJ11 leads to maturity-onset diabetes of the young (MODY) type 13, that is a subtype of dominant inherited young-onset non-autoimmune diabetes due to a primary defect in pancreatic beta cells. We generated induced pluripotent stem cells (iPSCs) from a patient with KCNJ11(p.Glu227Lys) mutation who developed MODY at 13years old. KCNJ11(p.Glu227Lys)-mutated cells that were reprogrammed by non-integrative viral transduction had normal karyotype, harboured the KCNJ11(p...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925364/generation-and-characterization-of-a-human-ipsc-line-from-a-patient-with-propionic-acidemia-due-to-defects-in-the-pcca-gene
#18
Esmeralda Alonso-Barroso, Sandra Brasil, Álvaro Briso-Montiano, Rosa Navarrete, Celia Pérez-Cerdá, Magdalena Ugarte, Belén Pérez, Lourdes R Desviat, Eva Richard
Human induced pluripotent stem cell (iPSC) line was generated from fibroblasts of a patient with propionic acidemia carrying mutations in the PCCA gene: c.1899+4_1899+7delAGTA; p.(Cys616_Val633del) and c.1430--?_1643+?del; p.(Gly477Glufs*9). Reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC were delivered using a non-integrative method based on the Sendai virus. Once established, iPSCs have shown full pluripotency, differentiation capacity and genetic stability.
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925363/generation-of-an-induced-pluripotent-stem-cell-line-from-a-patient-with-hereditary-multiple-endocrine-neoplasia-2b-men2b-syndrome-with-highest-risk-ret-mutation
#19
A Bennaceur-Griscelli, J Hadoux, O Féraud, P Opolon, D Divers, E Gobbo, M Schlumberger, F Griscelli, A G Turhan
Multiple Endocrine Neoplasia Type 2B (MEN2B) is a cancer-predisposing syndrome that affects patients with germline RET mutations. The clinical spectrum of the syndrome includes medullary thyroid carcinoma (MTC) and pheochromocytoma. Currently, there is no satisfactory model recapitulating all the features of the disease especially at the level of stem cells. We generated induced pluripotent stem cells (iPSCs) from a patient with RET mutation at codon 918 who developed pheochromocytoma and MTC. These iPSC had normal karyotype, harboured the RET(M918T) mutation and expressed pluripotency hallmarks...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925362/generation-of-a-klf15-homozygous-knockout-human-embryonic-stem-cell-line-using-paired-crispr-cas9n-and-human-cardiomyocytes-derivation
#20
Claudia Noack, Luis Peter Haupt, Wolfram-Hubertus Zimmermann, Katrin Streckfuss-Bömeke, Laura Cecilia Zelarayán
Krueppel-like factor 15 (KLF15) is abundantly expressed in liver, kidney, and muscle, including myocardium. In the adult heart KLF15 is important to maintain homeostasis and to repress hypertrophic remodeling. We generated a homozygous hESC KLF15 knockout (KO) line using paired CRISPR/Cas9n. KLF15-KO cells maintained full pluripotency and differentiation potential as well as genomic integrity. We demonstrated that KLF15-KO cells can be differentiated into morphologically normal cardiomyocytes turning them into a valuable tool for studying human KLF15-mediated mechanisms resulting in human cardiac dysfunction...
August 2017: Stem Cell Research
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