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human embryonic stem cells

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https://www.readbyqxmd.com/read/28445992/interaction-between-the-estrogen-receptor-and-fibroblast-growth-factor-receptor-pathways-in-non-small-cell-lung-cancer
#1
Jill M Siegfried, Mariya Farooqui, Natalie J Rothenberger, Sanja Dacic, Laura P Stabile
The estrogen receptor (ER) promotes non-small cell lung cancer (NSCLC) proliferation. Since fibroblast growth factors (FGFs) are known regulators of stem cell markers in ER positive breast cancer, we investigated whether a link between the ER, FGFs, and stem cell markers exists in NSCLC. In lung preneoplasias and adenomas of tobacco carcinogen exposed mice, the anti-estrogen fulvestrant and/or the aromatase inhibitor anastrozole blocked FGF2 and FGF9 secretion, and reduced expression of the stem cell markers SOX2 and nanog...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445466/human-pluripotent-stem-cells-recurrently-acquire-and-expand-dominant-negative-p53-mutations
#2
Florian T Merkle, Sulagna Ghosh, Nolan Kamitaki, Jana Mitchell, Yishai Avior, Curtis Mello, Seva Kashin, Shila Mekhoubad, Dusko Ilic, Maura Charlton, Genevieve Saphier, Robert E Handsaker, Giulio Genovese, Shiran Bar, Nissim Benvenisty, Steven A McCarroll, Kevin Eggan
Human pluripotent stem cells (hPS cells) can self-renew indefinitely, making them an attractive source for regenerative therapies. This expansion potential has been linked with the acquisition of large copy number variants that provide mutated cells with a growth advantage in culture. The nature, extent and functional effects of other acquired genome sequence mutations in cultured hPS cells are not known. Here we sequence the protein-coding genes (exomes) of 140 independent human embryonic stem cell (hES cell) lines, including 26 lines prepared for potential clinical use...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28444193/quantitative-assessment-of-timing-efficiency-specificity-and-genetic-mosaicism-of-crispr-cas9-mediated-gene-editing-of-hemoglobin-beta-gene-in-rhesus-monkey-embryos
#3
Uros Midic, Pei-Hsuan Hung, Kailey A Vincent, Benjamin Goheen, Patrick G Schupp, Diane D Chen, Daniel E Bauer, Catherine A VandeVoort, Keith E Latham
Gene editing technologies offer new options for developing novel biomedical research models and for gene and stem cell based therapies. However, applications in many species demand high efficiencies, specificity, and a thorough understanding of likely editing outcomes. To date, overall efficiencies, rates of off-targeting, and degree of genetic mosaicism have not been well-characterized for most species, limiting our ability to optimize methods. As a model gene for measuring these parameters of CRISPR/Cas9 application in a primate species (rhesus monkey), we selected the β-hemoglobin gene (HBB), which also has high relevance to potential application of gene editing and stem-cell technologies for treating human disease...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28442664/induction-of-neural-crest-cells-from-human-dental-pulp-derived-induced-pluripotent-stem-cells
#4
Eisuke Kawano, Taku Toriumi, Shinya Iguchi, Daigo Suzuki, Shuichi Sato, Masaki Honda
We previously generated induced pluripotent stem (iPS) cells from human dental pulp cells of deciduous teeth. Neural crest cells (NCCs) play a vital role in the development of the oral and maxillofacial region. Therefore, NCCs represent a cell source for bone, cartilage, and tooth-related tissue engineering. In this study, we examined whether iPS cells are capable of differentiating into NCCs through modification of the human embryonic stem cell protocol. First, iPS cells were dissociated into single cells and then reaggregated in low-cell-adhesion plates with neural induction medium for 8 days in suspension culture to form neurospheres...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28439102/mecp2-regulated-mirnas-control-early-human-neurogenesis-through-differential-effects-on-erk-and-akt-signaling
#5
N Mellios, D A Feldman, S D Sheridan, J P K Ip, S Kwok, S K Amoah, B Rosen, B A Rodriguez, B Crawford, R Swaminathan, S Chou, Y Li, M Ziats, C Ernst, R Jaenisch, S J Haggarty, M Sur
Rett syndrome (RTT) is an X-linked, neurodevelopmental disorder caused primarily by mutations in the methyl-CpG-binding protein 2 (MECP2) gene, which encodes a multifunctional epigenetic regulator with known links to a wide spectrum of neuropsychiatric disorders. Although postnatal functions of MeCP2 have been thoroughly investigated, its role in prenatal brain development remains poorly understood. Given the well-established importance of microRNAs (miRNAs) in neurogenesis, we employed isogenic human RTT patient-derived induced pluripotent stem cell (iPSC) and MeCP2 short hairpin RNA knockdown approaches to identify novel MeCP2-regulated miRNAs enriched during early human neuronal development...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28438190/very-small-embryonic-like-stem-cells-vsels-in-adult-mouse-uterine-perimetrium-and-myometrium
#6
Deepa Bhartiya, Kreema James
We have earlier reported the presence of very small embryonic-like stem cells (VSELs) in adult mouse uterus along with slightly bigger progenitors termed endometrial stem cells (EnSCs) and their regulation by ovarian hormones thus demonstrating a crucial role played by them during proliferation, differentiation and remodeling of the endometrium. Present study is a brief communication wherein we have examined the effect of higher dose of estrogen (E, 2 μg/day), progesterone (P, 1 mg/day) and follicle stimulating hormone (FSH, 5 IU/day for 5 days) specifically on the myometrium and perimetrium surrounding the endometrium in bilaterally ovariectomized mice...
April 24, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28436947/dedifferentiation-into-blastomere-like-cancer-stem-cells-via-formation-of-polyploid-giant-cancer-cells
#7
N Niu, I Mercado-Uribe, J Liu
Our recent perplexing findings that polyploid giant cancer cells (PGCCs) acquired embryonic-like stemness and were capable of tumor initiation raised two important unanswered questions: how do PGCCs acquire such stemness, and to which stage of normal development do PGCCs correspond. Intriguingly, formation of giant cells due to failed mitosis/cytokinesis is common in the blastomere stage of the preimplantation embryo. However, the relationship between PGCCs and giant blastomeres has never been studied. Here, we tracked the fate of single PGCCs following paclitaxel-induced mitotic failure...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436137/insights-into-in-vitro-spermatogenesis-in-mammals-past-present-future
#8
REVIEW
Amir Fattahi, Zeinab Latifi, Tohid Ghasemnejad, Hamid Reza Nejabati, Mohammad Nouri
Considering the self-renewal and differentiation ability of pluripotent stem cells, some studies have pointed out the possibility of stem cell-derived sperm production. Most studies that test this hypothesis have been conducted on rodents, with some promising results; however, studies on humans are progressing slowly, and have encountered technical and ethical hurdles. Established methods to differentiate stem cells - including embryoid bodies, co-culturing, and various feeder cells - may provide a niche that is similar to in vivo conditions and resolve epigenetic abnormalities, but a gonadal-like three-dimensional structure is still required to produce germ cells with the correct imprinting...
April 24, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28435121/proteome-analysis-of-human-embryonic-stem-cells-organelles
#9
Faezeh Shekari, Hossein Nezari, Mehran Rezaei Larijani, Chia-Li Han, Hossein Baharvand, Yu-Ju Chen, Ghasem Hosseini Salekdeh
As the functions of proteins are associated with their cellular localization, the comprehensive sub-cellular proteome knowledge of human embryonic stem cells (hESCs) is indispensable for ensuring a therapeutic effect. Here, we have utilized a sub-cellular proteomics approach to analyze the localization of proteins in the nucleus, mitochondria, crude membrane, cytoplasm, heavy and light microsomes. Out of 2002 reproducibly identified proteins, we detected 762 proteins in a single organelle whereas 160 proteins were found in all sub-cellular fractions...
April 20, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28434941/dysregulation-of-the-sirt1-oct6-axis-contributes-to-environmental-stress-induced-neural-induction-defects
#10
Guoping Li, Zeyidan Jiapaer, Rong Weng, Yi Hui, Wenwen Jia, Jiajie Xi, Guiying Wang, Songcheng Zhu, Xin Zhang, Dandan Feng, Ling Liu, Xiaoqing Zhang, Jiuhong Kang
Environmental stresses are increasingly acknowledged as core causes of abnormal neural induction leading to neural tube defects (NTDs). However, the mechanism responsible for environmental stress-triggered neural induction defects remains unknown. Here, we report that a spectrum of environmental stresses, including oxidative stress, starvation, and DNA damage, profoundly activate SIRT1, an NAD(+)-dependent lysine deacetylase. Both mouse embryos and in vitro differentiated embryonic stem cells (ESCs) demonstrated a negative correlation between the expression of SIRT1 and that of OCT6, a key neural fate inducer...
April 19, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28433654/high-molecular-weight-fgf2-isoforms-demonstrate-canonical-receptor-mediated-activity-and-support-human-embryonic-stem-cell-self-renewal
#11
Denis Kole, Alexandra Grella, David Dolivo, Lucia Shumaker, William Hermans, Tanja Dominko
Basic fibroblast growth factor (FGF2) is a highly pleiotropic member of a large family of growth factors with a broad range of activities, including mitogenesis and angiogenesis (Ornitz et al., 1996; Zhang et al., 2006), and it is known to be essential for maintenance of balance between survival, proliferation, and self-renewal in human pluripotent stem cells (Eiselleova et al., 2009; Zoumaro-Djayoon et al., 2011). A single FGF2 transcript can be translated into five FGF2 protein isoforms, an 18kDa low molecular weight (LMW) isoform and four larger high molecular weight (HMW) isoforms (Arese et al...
April 18, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28433627/docosahexaenoic-acid-promotes-differentiation-of-photoreceptor-cells-in-three-dimensional-neural-retinas
#12
Eisuke Arai, Vipul M Parmar, Bhubanananda Sahu, Lindsay Perusek, Tanu Parmar, Akiko Maeda
Retinal tissues generated from human pluripotent stem cells can be an excellent tool for investigating pathogenesis of retinal diseases and developing new pharmacologic therapies. Moreover, patient derived retinal tissues could allow for retinal transplantation therapy for degenerative retinal diseases. However, obtaining retinal tissues with matured photoreceptor outer segments, which are essential for photoreceptor functions, is currently challenging. Here we investigated the effects of docosahexaenoic acid (DHA) for maturation of photoreceptor outer segments at the late stage and visual chromophore analog, 9-cis-retinal for the early stage of differentiation to three-dimensional (3D)-retinal tissues from human embryonic stem cells (hESCs), respectively...
April 19, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28431857/modeling-human-infertility-with-pluripotent-stem-cells
#13
Di Chen, Joanna J Gell, Yu Tao, Enrique Sosa, Amander T Clark
Human fertility is dependent upon the correct establishment and differentiation of the germline. This is because no other cell type in the body is capable of passing a genome and epigenome from parent to child. Terminally differentiated germline cells in the adult testis and ovary are called gametes. However, the initial specification of germline cells occurs in the embryo around the time of gastrulation. Most of our knowledge regarding the cell and molecular events that govern human germline specification involves extrapolating scientific principles from model organisms, most notably the mouse...
April 13, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28430877/the-accessible-chromatin-landscape-during-conversion-of-human-embryonic-stem-cells-to-trophoblast-by-bmp4
#14
Yajun Liu, Dewu Ding, Hongde Liu, Xiao Sun
Human embryonic stem cells (hESC) exposed to the growth factor bone morphogenic protein 4 (BMP4) in the absence of FGF2 have been used as a model to study the development of placental development. However, little is known about the cis-regulatory mechanisms underlying this important process. In this study, we used the public available chromatin accessibility data of hESC H1 cells and BMP4-induced trophoblast (TB)cell lines to identify DNase I hypersensitive sites (DHSs) in the two cell lines, as well as the transcription factor binding sites within the DHSs...
April 18, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28430641/the-regulation-of-%C3%AE-catenin-activity-and-function-in-cancer-therapeutic-opportunities
#15
REVIEW
Shuang Shang, Fang Hua, Zhuo-Wei Hu
Wnt/β-catenin signaling is an evolutionarily conserved and versatile pathway that is known to be involved in embryonic development, tissue homeostasis and a wide variety of human diseases. Aberrant activation of this pathway gives rise to the accumulation of β-catenin in the nucleus and promotes the transcription of many oncogenes such as c-Myc and CyclinD-1. As a result, it contributes to carcinogenesis and tumor progression of several cancers, including colon cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429768/reassembling-embryos-in-vitro-from-component-stem-cells
#16
Caroline Kubaczka, George Q Daley
Researchers at the University of Cambridge, UK have succeeded in reconstructing mouse embryos by combining pluripotent embryonic and multipotent trophoblast stem cells in a 3D scaffold; the study from the laboratory of Professor Zernicka-Goetz, recently published in Science, provides a break-through tool to probe early mammalian development outside the uterus. Achieving a similar feat with human cells might necessitate reconsideration of the 14-day rule as a limitation of such research.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28429706/direct-comparison-of-distinct-naive-pluripotent-states-in-human-embryonic-stem-cells
#17
S Warrier, M Van der Jeught, G Duggal, L Tilleman, E Sutherland, J Taelman, M Popovic, S Lierman, S Chuva De Sousa Lopes, A Van Soom, L Peelman, F Van Nieuwerburgh, D I M De Coninck, B Menten, P Mestdagh, J Van de Sompele, D Deforce, P De Sutter, B Heindryckx
Until recently, human embryonic stem cells (hESCs) were shown to exist in a state of primed pluripotency, while mouse embryonic stem cells (mESCs) display a naive or primed pluripotent state. Here we show the rapid conversion of in-house-derived primed hESCs on mouse embryonic feeder layer (MEF) to a naive state within 5-6 days in naive conversion media (NCM-MEF), 6-10 days in naive human stem cell media (NHSM-MEF) and 14-20 days using the reverse-toggle protocol (RT-MEF). We further observe enhanced unbiased lineage-specific differentiation potential of naive hESCs converted in NCM-MEF, however, all naive hESCs fail to differentiate towards functional cell types...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28428263/different-requirements-of-functional-telomeres-in-neural-stem-cells-and-terminally-differentiated-neurons
#18
Anastasia Lobanova, Robert She, Simon Pieraut, Charlie Clapp, Anton Maximov, Eros Lazzerini Denchi
Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons...
April 20, 2017: Genes & Development
https://www.readbyqxmd.com/read/28427322/dental-pulp-pluripotent-like-stem-cells-dppsc-a-new-stem-cell-population-with-chromosomal-stability-and-osteogenic-capacity-for-biomaterials-evaluation
#19
Raquel Núñez-Toldrà, Ester Martínez-Sarrà, Carlos Gil-Recio, Miguel Ángel Carrasco, Ashraf Al Madhoun, Sheyla Montori, Maher Atari
BACKGROUND: Biomaterials are widely used to regenerate or substitute bone tissue. In order to evaluate their potential use for clinical applications, these need to be tested and evaluated in vitro with cell culture models. Frequently, immortalized osteoblastic cell lines are used in these studies. However, their uncontrolled proliferation rate, phenotypic changes or aberrations in mitotic processes limits their use in long-term investigations. Recently, we described a new pluripotent-like subpopulation of dental pulp stem cells derived from the third molars (DPPSC) that shows genetic stability and shares some pluripotent characteristics with embryonic stem cells...
April 21, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28426982/redox-environment-in-stem-and-differentiated-cells-a-quantitative-approach
#20
O G Lyublinskaya, Ju S Ivanova, N A Pugovkina, I V Kozhukharova, Z V Kovaleva, A N Shatrova, N D Aksenov, V V Zenin, Yu A Kaulin, I A Gamaley, N N Nikolsky
Stem cells are believed to maintain a specific intracellular redox status through a combination of enhanced removal capacity and limited production of ROS. In the present study, we challenge this assumption by developing a quantitative approach for the analysis of the pro- and antioxidant ability of human embryonic stem cells in comparison with their differentiated descendants, as well as adult stem and non-stem cells. Our measurements showed that embryonic stem cells are characterized by low ROS level, low rate of extracellular hydrogen peroxide removal and low threshold for peroxide-induced cytotoxicity...
April 11, 2017: Redox Biology
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