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human Embryonic stem cell

Lauren A Jevons, Franchesca D Houghton, Rahul S Tare
The rise in the incidence of musculoskeletal diseases is attributed to an increasing ageing population. The debilitating effects of musculoskeletal diseases, coupled with a lack of effective therapies, contribute to huge financial strains on healthcare systems. The focus of regenerative medicine has shifted to pluripotent stem cells (PSCs), namely, human embryonic stem cells and human-induced PSCs, due to the limited success of adult stem cell-based interventions. PSCs constitute a valuable cell source for musculoskeletal regeneration due to their capacity for unlimited self-renewal, ability to differentiate into all cell lineages of the three germ layers and perceived immunoprivileged characteristics...
March 20, 2018: Regenerative Medicine
Monia Cito, Silvia Pellegrini, Lorenzo Piemonti, Valeria Sordi
The experience in the field of islet transplantation shows that it is possible to replace β cells in a patient with type 1 diabetes (T1D), but this cell therapy is limited by the scarcity of organ donors and by the danger associated to the immunosuppressive drugs. Stem cell therapy is becoming a concrete opportunity to treat various diseases. In particular, for a disease like T1D, caused by the loss of a single specific cell type that does not need to be transplanted back in its originating site to perform its function, a stem cell-based cell replacement therapy seems to be the ideal cure...
March 2018: Endocrine Connections
Christina M Ferrer, Marielle Alders, Alex V Postma, Seonmi Park, Mark A Klein, Murat Cetinbas, Eva Pajkrt, Astrid Glas, Silvana van Koningsbruggen, Vincent M Christoffels, Marcel M A M Mannens, Lia Knegt, Jean-Pierre Etchegaray, Ruslan I Sadreyev, John M Denu, Gustavo Mostoslavsky, Merel C van Maarle, Raul Mostoslavsky
It has been well established that histone and DNA modifications are critical to maintaining the equilibrium between pluripotency and differentiation during early embryogenesis. Mutations in key regulators of DNA methylation have shown that the balance between gene regulation and function is critical during neural development in early years of life. However, there have been no identified cases linking epigenetic regulators to aberrant human development and fetal demise. Here, we demonstrate that a homozygous inactivating mutation in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses...
March 19, 2018: Genes & Development
Lyndon da Cruz, Kate Fynes, Odysseas Georgiadis, Julie Kerby, Yvonne H Luo, Ahmad Ahmado, Amanda Vernon, Julie T Daniels, Britta Nommiste, Shazeen M Hasan, Sakina B Gooljar, Amanda-Jayne F Carr, Anthony Vugler, Conor M Ramsden, Magda Bictash, Mike Fenster, Juliette Steer, Tricia Harbinson, Anna Wilbrey, Adnan Tufail, Gang Feng, Mark Whitlock, Anthony G Robson, Graham E Holder, Mandeep S Sagoo, Peter T Loudon, Paul Whiting, Peter J Coffey
Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)-derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more...
March 19, 2018: Nature Biotechnology
Michael J Ziller, Juan A Ortega, Katharina A Quinlan, David P Santos, Hongcang Gu, Eric J Martin, Christina Galonska, Ramona Pop, Susanne Maidl, Alba Di Pardo, Mei Huang, Herbert Y Meltzer, Andreas Gnirke, C J Heckman, Alexander Meissner, Evangelos Kiskinis
The somatic DNA methylation (DNAme) landscape is established early in development but remains highly dynamic within focal regions that overlap with gene regulatory elements. The significance of these dynamic changes, particularly in the central nervous system, remains unresolved. Here, we utilize a powerful human embryonic stem cell differentiation model for the generation of motor neurons (MNs) in combination with genetic mutations in the de novo DNAme machinery. We quantitatively dissect the role of DNAme in directing somatic cell fate with high-resolution genome-wide bisulfite-, bulk-, and single-cell-RNA sequencing...
March 14, 2018: Cell Stem Cell
Mousumi Sahu, Bibekanand Mallick
MicroRNAs (miRNAs) play crucial roles in pluripotency and differentiation of human Embryonic Stem Cells (hESCs). However, synergism among multiple miRNAs and their regulatory effects on stem cells are largely unknown. We investigated the synergistic regulations among miRNAs, which are differentially expressed in hESCs and fibroblasts (Fibs) to gain deeper insights into the regulatory mechanisms of miRNA-miRNA synergism in differentiation of hESCs into Fibs. In this study, we identified miRNA targets incorporating differential expression profiles of miRNAs and genes in hESCs-Fibs as well as miRNA targeting information followed by enrichment analysis...
March 14, 2018: International Journal of Biological Macromolecules
Peng Wang, San-Pin Wu, Kelsey E Brooks, Andrew M Kelleher, Jessica Milano-Foster, Francesco J DeMayo, Thomas E Spencer
Forkhead box A2 (FOXA2) is a pioneer transcription factor involved in organ development, function and cancer. In the uterus, FOXA2 is essential for pregnancy and expressed specifically in the glands of the endometrium loss of FOXA2 function occurs during development of endometrial cancer in humans. The present study describes the development of a mouse model for conditional expression of mouse FOXA2. Using a system consisting of a minigene located at the Rosa26 locus, a CAG-S-mFOXA2 allele was generated in embryonic stem cells and subsequently in mice; before activation, the minigene is silent due to a floxed stop cassette inserted between the promoter and the transgene...
March 13, 2018: Endocrinology
Minle Li, Keyu Gao, Laili Chu, Junnian Zheng, Jing Yang
Aurora kinase A (Aurora-A), a member of the Aurora family of serine/threonine kinases, plays a critical role in multiple steps of mitotic progression, including microtubule stability during the G1 phase of the cell cycle, chromosome alignment and segregation, and cytokinesis and is aberrantly expressed in various types of human cancers. In addition to its classic functions, recent studies have indicated that Aurora-A is critical for controlling self-renewal of embryonic stem cells through negative regulation of p53...
March 12, 2018: International Journal of Biochemistry & Cell Biology
Meixiang Zhang, Justine Ngo, Filomena Pirozzi, Ying-Pu Sun, Anthony Wynshaw-Boris
BACKGROUND: Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been widely used to generate cellular models harboring specific disease-related genotypes. Of particular importance are ESC and iPSC applications capable of producing dorsal telencephalic neural progenitor cells (NPCs) that are representative of the cerebral cortex and overcome the challenges of maintaining a homogeneous population of cortical progenitors over several passages in vitro. While previous studies were able to derive NPCs from pluripotent cell types, the fraction of dorsal NPCs in this population is small and decreases over several passages...
March 15, 2018: Stem Cell Research & Therapy
Alexandra J Harvey, Carmel O'Brien, Jack Lambshead, John R Sheedy, Joy Rathjen, Andrew L Laslett, David K Gardner
Reprogramming somatic cells to a pluripotent cell state (induced Pluripotent Stem (iPS) cells) requires reprogramming of metabolism to support cell proliferation and pluripotency, most notably changes in carbohydrate turnover that reflect a shift from oxidative to glycolytic metabolism. Some aspects of iPS cell metabolism differ from embryonic stem (ES) cells, which may reflect a parental cell memory, or be a consequence of the reprogramming process. In this study, we compared the metabolism of 3 human iPS cell lines to assess the fidelity of metabolic reprogramming...
2018: PloS One
Hongjiu Ren, Yitong Xu, Qiongzi Wang, Jun Jiang, Wudumuli, Linping Hui, Qingfu Zhang, Xiupeng Zhang, Enhua Wang, Limei Sun, Xueshan Qiu
Tripartite motif-containing (TRIM) 71 belongs to the TRIM protein family. Many studies have shown that TRIM71 plays conserved roles in stem cell proliferation, differentiation, and embryonic development; however, the relationship between TRIM71 and tumorigenesis is not clear. In this study, we demonstrate that TRIM71 expression in non-small cell lung cancer (NSCLC) is associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis. We found that TRIM71 was highly expressed in NSCLC cell lines compared with that in human normal bronchial epithelial cells...
February 16, 2018: Oncotarget
Yingqian Peng, Edouard Baulier, Yifeng Ke, Alejandra Young, Novruz B Ahmedli, Steven D Schwartz, Debora B Farber
Extracellular vesicles (EVs) released by virtually every cell of all organisms are involved in processes of intercellular communication through the delivery of their functional mRNAs, proteins and bioactive lipids. We previously demonstrated that mouse embryonic stem cell-released EVs (mESEVs) are able to transfer their content to different target retinal cells, inducing morphological and biochemical changes in them. The main objective of this paper is to characterize EVs derived from human embryonic stem cells (hESEVs) and investigate the effects that they have on cultured retinal glial, progenitor Müller cells, which are known to give rise to retinal neurons under specific conditions...
2018: PloS One
Ruichuan Yin, Jiezhen Mo, Jiayin Dai, Hailin Wang
Nickel is found widely in the environment. It is an essential microelement but also toxic. However, nickel displays only weak genotoxicity and mutagenicity. Exploration of the epigenetic toxicity of nickel is extremely interesting. Iron(ii)- and 2-oxoglutarate-dependent Tet dioxygenases are a class of epigenetic enzymes that catalyze the oxidation of DNA 5-methylcytosine (5mC). Thus, they are critical for DNA demethylation and, importantly, are involved with nuclear reprogramming, embryonic development, and regulation of gene expression...
March 14, 2018: Metallomics: Integrated Biometal Science
Halima Albalushi, Magdalena Kurek, Leif Karlsson, Luise Landreh, Kristín Rós Kjartansdóttir, Olle Söder, Outi Hovatta, Jan-Bernd Stukenborg
Human embryonic stem (hES) cells represent an important tool to study early cell development. The previously described use of human recombinant laminin (LN) 521 represented a step forward in generating clinically safe culture conditions. To test the short-term effect of LN521 on cultured hES cells, five male hES cell lines were cultured on human foreskin fibroblasts (hFFs), Matrigel, LN521, and LN121 and characterized by qPCR, immunofluorescence analysis, as well as their potential for three-germ layer differentiation...
2018: Stem Cells International
Buqing Ye, Benyu Liu, Liuliu Yang, Xiaoxiao Zhu, Dongdong Zhang, Wei Wu, Pingping Zhu, Yanying Wang, Shuo Wang, Pengyan Xia, Ying Du, Shu Meng, Guanling Huang, Jiayi Wu, Runsheng Chen, Yong Tian, Zusen Fan
Divergent long noncoding RNAs (lncRNAs) represent a major lncRNA biotype in mouse and human genomes. The biological and molecular functions of the divergent lncRNAs remain largely unknown. Here, we show that lncKdm2b , a divergent lncRNA for Kdm2b gene, is conserved among five mammalian species and highly expressed in embryonic stem cells (ESCs) and early embryos. LncKdm2b knockout impairs ESC self-renewal and causes early embryonic lethality. LncKdm2b can activate Zbtb3 by promoting the assembly and ATPase activity of Snf2-related CREBBP activator protein (SRCAP) complex in trans Zbtb3 potentiates the ESC self-renewal in a Nanog-dependent manner...
March 13, 2018: EMBO Journal
Wyatt E Lanik, Madison A Mara, Belgacem Mihi, Carolyn B Coyne, Misty Good
Studies on the intestinal epithelial response to viral infection have previously been limited by the absence of in vitro human intestinal models that recapitulate the multicellular complexity of the gastrointestinal tract. Recent technological advances have led to the development of "mini-intestine" models, which mimic the diverse cellular nature and physiological activity of the small intestine. Utilizing adult or embryonic intestinal tissue, enteroid and organoid systems, respectively, represent an opportunity to effectively model cellular differentiation, proliferation, and interactions that are specific to the specialized environment of the intestine...
March 10, 2018: Viruses
Wasco Wruck, James Adjaye
Induced pluripotent stem cells (iPSCs) and human embryonic stem cells (hESCs) differentiated into hepatocyte-like cells (HLCs) provide a defined and renewable source of cells for drug screening, toxicology and regenerative medicine. We previously reprogrammed human fetal foreskin fibroblast cells (HFF1) into iPSCs employing an episomal plasmid-based integration-free approach, this iPSC-line and the hESC lines H1 and H9 were used to model hepatogenesis in vitro. Biochemical characterisation confirmed glycogen storage, ICG uptake and release, urea and bile acid production, as well as CYP3A4 activity...
March 13, 2018: Scientific Data
Liu-Lin Xiong, Yu Zou, Yu Shi, Piao Zhang, Rong-Ping Zhang, Xie-Jie Dai, Bin Liu, Ting-Hua Wang
The aim of the present study was to determine the effect of implanted neural stem cells (NSCs) on the functional recovery of tree shrews (TSs) subjected to hemi‑sectioned spinal cord injury (hSCI), and to investigate the possible mechanism involved. NSCs (passage 2), derived from the hippocampus of TSs (embryonic day 20), were labeled with Hoechst 33342 and transplanted intraspinally into the hSC of TSs at thoracic level 10 in the acute (immediately after injury) and chronic (day 9 post‑injury) stages...
March 9, 2018: International Journal of Molecular Medicine
Yangyang Ma, Tong Yu, Yuanxing Cai, Huayan Wang
Derivation of bona fide porcine pluripotent stem cells is still a critical issue because porcine embryonic stem cells (ESCs) are not available yet, and most of the culture conditions to maintain porcine induced pluripotent stem cells (piPSCs) are based on conditions for mouse and human iPS cells. In this study, we generated a doxycycline-inducible porcine iPS cell line (DOX-iPSCs) and used it to screen the optimal culture condition to sustain the self-renewal of piPSCs. We found that LIF and b-FGF were required for porcine cell reprogramming, but were not essential cytokines for maintaining the self-renewal and pluripotency of piPSCs...
December 2018: Cell Death Discovery
Jocelyn Charlton, Timothy L Downing, Zachary D Smith, Hongcang Gu, Kendell Clement, Ramona Pop, Veronika Akopian, Sven Klages, David P Santos, Alexander M Tsankov, Bernd Timmermann, Michael J Ziller, Evangelos Kiskinis, Andreas Gnirke, Alexander Meissner
Cytosine methylation is widespread among organisms and essential for mammalian development. In line with early postulations of an epigenetic role in gene regulation, symmetric CpG methylation can be mitotically propagated over many generations with extraordinarily high fidelity. Here, we combine BrdU labeling and immunoprecipitation with genome-wide bisulfite sequencing to explore the inheritance of cytosine methylation onto newly replicated DNA in human cells. Globally, we observe a pronounced lag between the copying of genetic and epigenetic information in embryonic stem cells that is reconsolidated within hours to accomplish faithful mitotic transmission...
March 12, 2018: Nature Structural & Molecular Biology
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