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https://www.readbyqxmd.com/read/28102845/h19-let-7-lin28-reciprocal-negative-regulatory-circuit-promotes-breast-cancer-stem-cell-maintenance
#1
Fei Peng, Ting-Ting Li, Kai-Li Wang, Guo-Qing Xiao, Ju-Hong Wang, Hai-Dong Zhao, Zhi-Jie Kang, Wen-Jun Fan, Li-Li Zhu, Mei Li, Bai Cui, Fei-Meng Zheng, Hong-Jiang Wang, Eric W-F Lam, Bo Wang, Jie Xu, Quentin Liu
Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28102837/precise-and-efficient-scarless-genome-editing-in-stem-cells-using-correct
#2
Dylan Kwart, Dominik Paquet, Shaun Teo, Marc Tessier-Lavigne
CRISPR/Cas9 is a promising tool for genome-editing DNA in cells with single-base-pair precision, which allows novel in vitro models of human disease to be generated-e.g., in pluripotent stem cells. However, the accuracy of intended sequence changes can be severely diminished by CRISPR/Cas9's propensity to re-edit previously modified loci, causing unwanted mutations (indels) alongside intended changes. Here we describe a genome-editing framework termed consecutive re-guide or re-Cas steps to erase CRISPR/Cas-blocked targets (CORRECT), which, by exploiting the use of highly efficacious CRISPR/Cas-blocking mutations in two rounds of genome editing, enables accurate, efficient and scarless introduction of specific base changes-for example, in human induced pluripotent (iPS) stem cells...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28102490/genome-engineering-of-stem-cell-organoids-for-disease-modeling
#3
REVIEW
Yingmin Sun, Qiurong Ding
Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized disease information and recapitulate disease development processes at the molecular, cellular and organ levels. With recent development in stem cell field, a variety of tissue organoids can be derived from patient specific pluripotent stem cells and adult stem cells. In combination with the state-of-the-art genome editing tools, organoids can be further engineered to mimic disease-relevant genetic and epigenetic status of a patient...
January 19, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28101702/bone-marrow-very-small-embryonic-like-stem-cells-new-generation-of-autologous-cell-therapy-soon-ready-for-prime-time
#4
EDITORIAL
David M Smadja
Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells described in human and mouse. In this issue of Stem Cell Reviews and Reports, Shaikh and colleagues show in a valuable work that mouse bone marrow collected after 5FU treatment contains VSELs able to undergo in vitro multi-lineage differentiation into cells from all three germ layers and also in germ and hematopoietic cells. These findings are robust since no confounding factor such as feeder cell fusion with VSELs can occur here...
January 18, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28101336/regulatory-elements-and-transcriptional-control-of-chicken-vasa-homologue-cvh-promoter-in-chicken-primordial-germ-cells
#5
So Dam Jin, Bo Ram Lee, Young Sun Hwang, Hong Jo Lee, Jong Seop Rim, Jae Yong Han
BACKGROUND: Primordial germ cells (PGCs), the precursors of functional gametes, have distinct characteristics and exhibit several unique molecular mechanisms to maintain pluripotency and germness in comparison to somatic cells. They express germ cell-specific RNA binding proteins (RBPs) by modulating tissue-specific cis- and trans-regulatory elements. Studies on gene structures of chicken vasa homologue (CVH), a chicken RNA binding protein, involved in temporal and spatial regulation are thus important not only for understanding the molecular mechanisms that regulate germ cell fate, but also for practical applications of primordial germ cells...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28100686/noncanonical-function-of-dgcr8-controls-mesc-exit-from-pluripotency
#6
Daniel Cirera-Salinas, Jian Yu, Maxime Bodak, Richard P Ngondo, Kristina M Herbert, Constance Ciaudo
Mouse embryonic stem cells (mESCs) deficient for DGCR8, a key component of the microprocessor complex, present strong differentiation defects. However, the exact reasons impairing their commitment remain elusive. The analysis of newly generated mutant mESCs revealed that DGCR8 is essential for the exit from the pluripotency state. To dissociate canonical versus noncanonical functions of DGCR8, we complemented the mutant mESCs with a phosphomutant DGCR8, which restored microRNA levels but did not rescue the exit from pluripotency defect...
January 18, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28100040/induced-pluripotent-stem-cell-research-in-the-era-of-precision-medicine
#7
Takashi Hamazaki, Nihal El Rouby, Natalie C Fredette, Katherine E Santostefano, Naohiro Terada
Recent advances in DNA sequencing technologies are revealing how human genetic variations associate with differential health risks, disease susceptibilities and drug responses. Such information is now expected to help evaluate individual health risks, design personalized health plans and treat patients with precision. It is still challenging, however, to understand how such genetic variations cause the phenotypic alterations in pathobiologies and treatment response. Human induced pluripotent stem cell (iPSC) technologies are emerging as a promising strategy to fill the knowledge gaps between genetic association studies and underlying molecular mechanisms...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28100021/identifying-the-biphasic-role-of-calcineurin-nfat-signaling-enables-replacement-of-sox2-in-somatic-cell-reprogramming
#8
Sherif Khodeer, Takumi Era
Induction of pluripotency with defined factors (Oct4, Sox2, Klf4, c-Myc) raises hopes for successful clinical trials. Despite considerable efforts, the molecular mechanism of reprogramming remains poorly understood. The aim of the present study was to identify the role of calcineurin/nuclear factor of activated T cells (NFAT) in reprogramming. Our results demonstrated a biphasic role for calcineurin/NFAT signaling during reprogramming. In the early phase of reprogramming, calcineurin activity is required to maintain proper cell cycle division and for mesenchymal-epithelial transition...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28098961/angiogenic-and-osteogenic-regeneration-in-rats-via-calcium-phosphate-scaffold-and-endothelial-cell-coculture-with-hbmscs-hucmscs-hipsc-mscs-and-hesc-mscs
#9
Wenchuan Chen, Xian Liu, Qianmin Chen, Chongyun Bao, Liang Zhao, Zhimin Zhu, Hockin H K Xu
Angiogenesis is a limiting factor in regenerating large bone defects. The objective of this study was to investigate angiogenic and osteogenic effects of coculture on calcium phosphate cement (CPC) scaffold using human umbilical vein endothelial cells (hUVECs) and mesenchymal stem cells (MSCs) from different origins for the first time. hUVECs were cocultured with four types of cells: human umbilical cord MSCs (hUCMSCs), human bone marrow MSCs (hBMSCs), and MSCs from induced pluripotent stem cells (hiPSC-MSCs) and embryonic stem cells (hESC-MSCs)...
January 18, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28097777/activin-a-in-combination-with-erk1-2-mapk-pathway-inhibition-sustains-propagation-of-mouse-embryonic-stem-cells
#10
Yuhei Ashida, May Nakajima-Koyama, Akira Hirota, Takuya Yamamoto, Eisuke Nishida
The Activin/Nodal/TGF-β signaling pathway plays a major role in maintaining mouse epiblast stem cells (EpiSCs). The EpiSC-maintaining medium, which contains Activin A and bFGF, induces differentiation of mouse embryonic stem cells (ESCs) to EpiSCs. Here, we show that Activin A also has an ability to efficiently propagate ESCs without differentiation to EpiSCs when combined with a MEK inhibitor PD0325901. ESCs cultured in Activin+PD retained high-level expression of naive pluripotency-related transcription factors...
January 18, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28097227/a-xenogeneic-free-system-generating-functional-human-gut-organoids-from-pluripotent-stem-cells
#11
Hajime Uchida, Masakazu Machida, Takumi Miura, Tomoyuki Kawasaki, Takuya Okazaki, Kengo Sasaki, Seisuke Sakamoto, Noriaki Ohuchi, Mureo Kasahara, Akihiro Umezawa, Hidenori Akutsu
Functional intestines are composed of cell types from all 3 primary germ layers and are generated through a highly orchestrated and serial developmental process. Directed differentiation of human pluripotent stem cells (hPSCs) has been shown to yield gut-specific cell types; however, these structures do not reproduce critical functional interactions between cell types of different germ layers. Here, we developed a simple protocol for the generation of mature functional intestinal organoids from hPSCs under xenogeneic-free conditions...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28096337/stress-granule-associated-protein-g3bp2-regulates-breast-tumor-initiation
#12
Nisha Gupta, Mark Badeaux, Yiqian Liu, Kamila Naxerova, Dennis Sgroi, Lance L Munn, Rakesh K Jain, Igor Garkavtsev
Breast tumors contain tumorigenic cancer cells, termed "tumor-initiating cells" (TICs), which are capable of both replenishing themselves and giving rise to populations of nontumorigenic breast cancer cells (non-TICs). However, the molecular mechanisms responsible for breast tumor initiation remain poorly understood. Here we describe a chemical screening strategy to identify small molecules that enhance the effect of chemotherapeutic agents on TIC-enriched breast cancer cells. We identified proteins that interact with the lead compound C108, including the stress granule-associated protein, GTPase-activating protein (SH3 domain)-binding protein 2, G3BP2...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096308/-re-building-a-kidney
#13
Leif Oxburgh, Thomas J Carroll, Ondine Cleaver, Daniel R Gossett, Deborah K Hoshizaki, Jeffrey A Hubbell, Benjamin D Humphreys, Sanjay Jain, Jan Jensen, David L Kaplan, Carl Kesselman, Christian J Ketchum, Melissa H Little, Andrew P McMahon, Stuart J Shankland, Jason R Spence, M Todd Valerius, Jason A Wertheim, Oliver Wessely, Ying Zheng, Iain A Drummond
(Re)Building a Kidney is a National Institute of Diabetes and Digestive and Kidney Diseases-led consortium to optimize approaches for the isolation, expansion, and differentiation of appropriate kidney cell types and the integration of these cells into complex structures that replicate human kidney function. The ultimate goals of the consortium are two-fold: to develop and implement strategies for in vitro engineering of replacement kidney tissue, and to devise strategies to stimulate regeneration of nephrons in situ to restore failing kidney function...
January 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28096214/cartilage-to-bone-transformation-during-fracture-healing-is-coordinated-by-the-invading-vasculature-and-induction-of-the-core-pluripotency-genes
#14
Diane P Hu, Federico Ferro, Frank Yang, Aaron J Taylor, Wenhan Chang, Theodore Miclau, Ralph S Marcucio, Chelsea S Bahney
Fractures heal predominantly through the process of endochondral ossification. The classic model of endochondral ossification holds that chondrocytes mature to hypertrophy, undergo apoptosis and new bone forms by invading osteoprogenitors. However, recent data demonstrate that chondrocytes transdifferentiate to osteoblasts in the growth plate and during regeneration, yet the mechanism(s) regulating this process remain unknown. Here, we show a spatially-dependent phenotypic overlap between hypertrophic chondrocytes and osteoblasts at the chondro-osseous border in the fracture callus, in a region we define as the transition zone (TZ)...
January 15, 2017: Development
https://www.readbyqxmd.com/read/28096211/primate-embryogenesis-predicts-the-hallmarks-of-human-na%C3%A3-ve-pluripotency
#15
REVIEW
Thorsten Boroviak, Jennifer Nichols
Naïve pluripotent mouse embryonic stem cells (ESCs) resemble the preimplantation epiblast and efficiently contribute to chimaeras. Primate ESCs correspond to the postimplantation embryo and fail to resume development in chimaeric assays. Recent data suggest that human ESCs can be 'reset' to an earlier developmental stage, but their functional capacity remains ill defined. Here, we discuss how the naïve state is inherently linked to preimplantation epiblast identity in the embryo. We hypothesise that distinctive features of primate development provide stringent criteria to evaluate naïve pluripotency in human and other primate cells...
January 15, 2017: Development
https://www.readbyqxmd.com/read/28096185/transcriptomic-profiling-of-purified-patient-derived-dopamine-neurons-identifies-convergent-perturbations-and-therapeutics-for-parkinson-s-disease
#16
Cynthia Sandor, Paul Robertson, Charmaine Lang, Andreas Heger, Heather Booth, Jane Vowles, Lorna Witty, Rory Bowden, Michele Hu, Sally A Cowley, Richard Wade-Martins, Caleb Webber
While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes...
January 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28095419/prc2-represses-hormone-induced-somatic-embryogenesis-in-vegetative-tissue-of-arabidopsis-thaliana
#17
Iva Mozgová, Rafael Muñoz-Viana, Lars Hennig
Many plant cells can be reprogrammed into a pluripotent state that allows ectopic organ development. Inducing totipotent states to stimulate somatic embryo (SE) development is, however, challenging due to insufficient understanding of molecular barriers that prevent somatic cell dedifferentiation. Here we show that Polycomb repressive complex 2 (PRC2)-activity imposes a barrier to hormone-mediated transcriptional reprogramming towards somatic embryogenesis in vegetative tissue of Arabidopsis thaliana. We identify factors that enable SE development in PRC2-depleted shoot and root tissue and demonstrate that the establishment of embryogenic potential is marked by ectopic co-activation of crucial developmental regulators that specify shoot, root and embryo identity...
January 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28094846/chronic-drug-induced-effects-on-contractile-motion-properties-and-cardiac-biomarkers-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#18
Ivan Kopljar, An De Bondt, Petra Vinken, Ard Teisman, Bruce Damiano, Nick Goeminne, Ilse Van den Wyngaert, David J Gallacher, Hua Rong Lu
BACKGROUND AND PURPOSE: Risk assessment of chronic cardiac safety liabilities within the pharmaceutical industry is mostly performed during late stages of pre-clinical drug development using in vivo animal models. Here, we explored the potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to detect chronic cardiac risks such as drug-induced cardiomyocyte toxicity. EXPERIMENTAL APPROACH: Video microscopy-based motion field imaging was applied to evaluate chronic effect (over 72 h) of cardiotoxic drugs on the contractile motion of hiPS-CMs...
January 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28094826/response-to-dittrich-et-al-non-embryo-destructive-extraction-of-pluripotent-embryonic-stem-cells-overlooked-legal-prohibitions-professional-legal-consequences-and-inconsistencies-in-patent-law
#19
REVIEW
T Faltus, U Storz
The publication of "Non-embryo-destructive Extraction of Pluripotent Embryonic Stem Cells: Implications for Regenerative Medicine and Reproductive Medicine" by Dittrich et al. in Geburtshilfe und Frauenheilkunde 2015; 75: 1239-1242 1 describes various possibilities which could result from the non-embryo-destructive extraction of embryonic stem cells from human blastocysts. But implementing this method is more problematic, both legally and ethically, than the authors have represented it to be and is illegal in Germany...
December 2016: Geburtshilfe und Frauenheilkunde
https://www.readbyqxmd.com/read/28093523/cutting-edge-nanog-activates-autophagy-under-hypoxic-stress-by-binding-to-bnip3l-promoter
#20
Meriem Hasmim, Bassam Janji, Mehdi Khaled, Muhammad Zaeem Noman, Fawzia Louache, Didier Bordereaux, Abdou Abderamane, Veronique Baud, Fathia Mami-Chouaib, Salem Chouaib
Hypoxia upregulates the core pluripotency factors NANOG, SOX2, and OCT4, associated with tumor aggressiveness and resistance to conventional anticancer treatments. We have previously reported that hypoxia-induced NANOG contributed in vitro to tumor cell resistance to autologous-specific CTL and in vivo to the in situ recruitment of immune-suppressive cells. In this study, we investigated the mechanisms underlying NANOG-mediated tumor cell resistance to specific lysis under hypoxia. We demonstrated the tumor-promoting effect of hypoxia on tumor initiation into immunodeficient mice using human non-small lung carcinoma cells...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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