Featured
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Letter |
Derivation of novel human ground state naive pluripotent stem cells
It is known that human embryonic stem (ES) cells are more similar to mouse primed epiblast stem cells than to naive mouse ES cells; here culture conditions are determined that allow human ES and induced pluripotent stem cells to acquire a pluripotent state that retains growth characteristics highly similar to mouse naive ES cells, and competence in generating cross-species human-mouse embryonic chimaerism.
- Ohad Gafni
- , Leehee Weinberger
- & Jacob H. Hanna
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Article |
Deterministic direct reprogramming of somatic cells to pluripotency
This study shows that the combination of naive pluripotency growth conditions, Oct4, Sox2, Klf4 and Myc (OSKM) overexpression, and depleting the Mbd3/NuRD co-repressor results in deterministic and synchronized reprogramming to pluripotency.
- Yoach Rais
- , Asaf Zviran
- & Jacob H. Hanna
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Letter |
Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture
A new approach has been developed in order to achieve the stepwise differentiation of inner ear sensory epithelia from mouse embryonic stem cells in a three-dimensional culture: this process, which mimics normal development and produces cells that have functional characteristics of mechanosensitive hair cells, is hoped to provide further insights into inner ear development and disorder.
- Karl R. Koehler
- , Andrew M. Mikosz
- & Eri Hashino
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Article |
Myc-driven endogenous cell competition in the early mammalian embryo
An in vivo genetic approach to generate mosaic expression of Myc in the mouse epiblast reveals evidence of cell competition, a tissue homeostasis mechanism first described in Drosophila by which viable but suboptimal cells are eliminated from metazoan tissues; during normal development Myc expression levels in the epiblast are heterogeneous, and endogenous cell competition refines the epiblast cell population through the apoptotic elimination of cells with low relative Myc levels.
- Cristina Clavería
- , Giovanna Giovinazzo
- & Miguel Torres
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Letter |
Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells
Vitamin C is a direct regulator of Tet enzyme activity and DNA methylation fidelity in mouse ES cells; addition of vitamin C promotes Tet activity, increases 5-hydroxymethlycytosine (5hmC) and DNA demethylation of many gene promoters, upregulates demethylated germline genes, and induces a state that more closely approximates that of the inner cell mass of the blastocyst.
- Kathryn Blaschke
- , Kevin T. Ebata
- & Miguel Ramalho-Santos
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Letter |
A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28–let-7 pathway
This study shows that Dis3l2 is the 3′–5′ exonuclease that mediates the degradation of uridylated precursor let-7 microRNA; this is the first physiological RNA substrate identified for this new exonuclease, which causes the Perlman syndrome of fetal overgrowth and Wilms’ tumour susceptibility when mutated.
- Hao-Ming Chang
- , Robinson Triboulet
- & Richard I. Gregory
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News & Views |
Stem cells bear eggs
Researchers have coaxed cultured embryonic stem cells to develop into eggs that then give rise to normal offspring. The discovery should help to decode the molecular basis of gamete formation and might lead to treatments for infertility.
- Sihem Cheloufi
- & Konrad Hochedlinger
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Research Highlights |
Mouse eggs from stem cells
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Letter |
Androgenetic haploid embryonic stem cells produce live transgenic mice
Mouse androgenetic haploid embryonic stem cell lines can be established by transferring sperm into an enucleated oocyte; the cells maintain haploidy and stable growth over 30 passages, express pluripotent markers, are able to differentiate into all three germ layers, contribute to germlines of chimaeras when injected into blastocysts and can produce fertile progeny that carry genetic modifications to the next generation.
- Wei Li
- , Ling Shuai
- & Qi Zhou
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Letter |
Restoration of auditory evoked responses by human ES-cell-derived otic progenitors
Two types of human ES-cell-derived otic progenitors are shown to have the ability to differentiate in vitro into hair-cell-like cells and auditory neurons, and to engraft, differentiate and improve auditory-evoked response thresholds when transplanted into an auditory neuropathy model; this indicates that it may be possible to use cell-based therapeutic strategies to recover damaged sensory circuitry in deafness.
- Wei Chen
- , Nopporn Jongkamonwiwat
- & Marcelo N. Rivolta
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Letter |
Increased proteasome activity in human embryonic stem cells is regulated by PSMD11
Human embryonic stem cells (hESCs) are shown to have high 26S/30S proteasome activity owing to increased expression of the 19S proteasome subunit PSMD11; FOXO4 regulates proteasome activity in hESCs by modulating PSMD11 expression, and the high proteasome activity decreases after induced differentiation.
- David Vilchez
- , Leah Boyer
- & Andrew Dillin
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News Feature |
Tissue engineering: The brainmaker
With his knack for knowing what stem cells want, Yoshiki Sasai has grown an eye and parts of a brain in a dish.
- David Cyranoski
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Letter |
Human ES-cell-derived cardiomyocytes electrically couple and suppress arrhythmias in injured hearts
A guinea-pig model of cardiac injury is used to show that human embryonic stem-cell-derived cardiomyocyte grafts can electrically integrate into the injured heart, improving mechanical function and reducing spontaneous and induced ventricular tachycardia; this is a major step towards clinical adoption of cell replacement therapies for cardiovascular diseases using human cardiomyocytes.
- Yuji Shiba
- , Sarah Fernandes
- & Michael A. Laflamme
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News & Views |
A sporadic super state
It seems that embryonic stem cells regularly pass through a transient state during which they can generate all the cell types of an animal, including those of the placenta. See Article p.57
- Azim Surani
- & Julia Tischler
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Article |
Embryonic stem cell potency fluctuates with endogenous retrovirus activity
A rare cell subpopulation within mouse embryonic stem cell cultures is identified that exhibits properties of two-cell (2C) embryos; the interconversion of ES cells to 2C cells correlates with endogenous retroviral activity.
- Todd S. Macfarlan
- , Wesley D. Gifford
- & Samuel L. Pfaff
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Research Highlights |
Recipes for making lung cells
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Article |
Ubiquitin-dependent regulation of COPII coat size and function
The size of COPII vesicles is shown to be controlled by monoubiquitylation, with potential implications for cranio-lenticulo-sutural dysplasia and chylomicron retention disease.
- Lingyan Jin
- , Kanika Bajaj Pahuja
- & Michael Rape
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Letter |
Control of ground-state pluripotency by allelic regulation of Nanog
Tight regulation of Nanog dose at the chromosome level is important for the acquisition of pluripotency during development.
- Yusuke Miyanari
- & Maria-Elena Torres-Padilla
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Editorial |
Error of judgment
The European Court of Justice was wrong to weigh in on the definition of a human embryo.
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News Feature |
Stem cells: The cell division
Oliver Brüstle fought for more than a decade to pursue and patent human embryonic stem-cell research in Germany. Now his efforts have backfired.
- Alison Abbott
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Article |
DNA-binding factors shape the mouse methylome at distal regulatory regions
Base-pair-resolution genomic maps of DNA methylation are generated in the mouse, providing new insights in gene regulation.
- Michael B. Stadler
- , Rabih Murr
- & Dirk Schübeler
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News |
Stem cells that are pure enough for the clinic
High-quality human embryonic stem cells derived without the use of animal products.
- Ewen Callaway
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News & Views |
Organ recital in a dish
It is difficult to recapitulate organ development in vitro, especially when interactions between tissues are essential. Nonetheless, researchers have now achieved this for the pituitary gland. See Article p.57
- Karine Rizzoti
- & Robin Lovell-Badge
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News |
Stem-cell pioneer bows out
Geron halts first-of-its-kind clinical trial for spinal therapy.
- Monya Baker
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News |
Host neurons obey transplants
Neurons derived from human embryonic stem cells can control native neurons in mice.
- Charlotte Schubert
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Article |
Self-formation of functional adenohypophysis in three-dimensional culture
Mouse embryonic stem cells are induced to form functional anterior pituitary tissue in three-dimensional culture.
- Hidetaka Suga
- , Taisuke Kadoshima
- & Yoshiki Sasai
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Letter |
Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease
A new strategy for derivation of human midbrain dopamine neurons from pluripotent cells was developed; transplantation of the neurons in mice, rats and parkinsonian monkeys show they are a promising source of cells for applications in regenerative medicine.
- Sonja Kriks
- , Jae-Won Shim
- & Lorenz Studer
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News |
European ban on stem-cell patents has a silver lining
Researchers can work without fear of action over patent infringement.
- Ewen Callaway
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News |
European court bans patents based on embryonic stem cells
Final decision could stifle investment in developing therapies.
- Ewen Callaway
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News |
Cloned human embryo makes working stem cells
Researchers begin to identify past problems with cloning technique.
- David Cyranoski
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Article |
lincRNAs act in the circuitry controlling pluripotency and differentiation
- Mitchell Guttman
- , Julie Donaghey
- & Eric S. Lander
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News & Views |
Bespoke cells for the human brain
Human skin cells have been directly converted into neurons, an achievement that could lead to the cell-based treatment of neurodegenerative disorders. But the road ahead remains long and tortuous. See Letters p.220, p.224 & p.228
- Michael Sendtner
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News |
Court quashes stem-cell lawsuit
US judge throws out case meant to halt federal funding, but research remains vulnerable.
- Meredith Wadman
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News & Views |
Tet proteins in the limelight
Tet proteins mediate the hydroxymethylation of DNA. New work reveals their function in gene regulation and the extent of their activity throughout the genome of embryonic stem cells. See Article p.343 & Letters p.389, p.394 & p.398
- Nathalie Véron
- & Antoine H. F. M. Peters
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Letter |
Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells
- William A. Pastor
- , Utz J. Pape
- & Anjana Rao
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Article |
Self-organizing optic-cup morphogenesis in three-dimensional culture
Organogenesis relies on the orchestration of many cellular interactions to create the collective cell behaviours that progressively shape developing tissues. Using a three-dimensional embryonic stem cell culture system, this study successfully generated neural retinal tissues that formed a fully stratified neural retinal structure with all the major components located in their proper spatial location as seen during optic-cup development in vivo. This approach might have important implications for stem cell therapy for retinal repair.
- Mototsugu Eiraku
- , Nozomu Takata
- & Yoshiki Sasai
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Letter |
Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation
- Gabriella Ficz
- , Miguel R. Branco
- & Wolf Reik
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Letter |
Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells
- Hao Wu
- , Ana C. D’Alessio
- & Yi Zhang
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News |
Flaw in induced-stem-cell model
Adult cells do not fully convert to embryonic-like state.
- Elie Dolgin
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News |
France mulls embryo research reform
Scientists and clinicians push for a clearer, more permissive law on human embryonic stem-cell work.
- Declan Butler
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Letter |
A unique chromatin signature uncovers early developmental enhancers in humans
Identifying the genomic regulatory sequences, such as enhancers, that control early embryonic development remains a difficult challenge. Here, profiling of histone modifications and chromatin regulators in human embryonic stem cells (hESCs) reveals unique signatures that are used to identify over 2,000 putative enhancers. These enhancers are either active in the h ESCs or associated with early developmental genes.
- Alvaro Rada-Iglesias
- , Ruchi Bajpai
- & Joanna Wysocka
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News |
Human intestinal tissue grown in the lab
The technique could be used to study disease and tailor therapies.
- Janelle Weaver
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Letter |
Molecular coupling of Tsix regulation and pluripotency
Reprogramming of X-chromosome inactivation during the acquisition of pluripotency is accompanied by repression of Xist, the trigger of X-inactivation, and by upregulation of its antisense counterpart, Tsix. In undifferentiated embryonic stem cells (ESCs), key transcription factors that support pluripotency repress Xist transcription. These authors show that upregulation of Tsix in ESCs depends on a different subset of pluripotency factors. Therefore, two distinct ESC-specific complexes couple reprogramming of X-inactivation to pluripotency.
- Pablo Navarro
- , Andrew Oldfield
- & Philip Avner
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Letter |
Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice
Two forms of X-chromosome inactivation ensure the selective silencing of female sex chromosomes in mouse embryos. Imprinted silencing begins with the detection of Xist RNA expression on the paternal X chromosome at about the four-cell stage of development. Later, a random form of inactivation silences either the paternal or the maternal X chromosome. Here it is shown that maternal deposits of the ubiquitin ligase Rnf12/RLIM are required for the imprinted form of X-chromosome inactivation.
- JongDae Shin
- , Michael Bossenz
- & Ingolf Bach
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Letter |
A genome-wide RNAi screen reveals determinants of human embryonic stem cell identity
Realizing the full potential of human embryonic stem cells (hESCs) in research and clinical applications requires a detailed understanding of the genetic network that governs their unique properties. A genome-wide RNA interference screen identifies a wealth of new regulators of self-renewal and pluripotency properties in hESCs. The transcription factor PRDM14, for example, is required for the maintenance of hESC identity and reprogramming of somatic cells to pluripotency.
- Na-Yu Chia
- , Yun-Shen Chan
- & Huck-Hui Ng
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News |
Stem cells: A legal round table
Our expert panel examines the recent stem cell injunction from all angles.
- Meredith Wadman