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Low-grade chromosomal mosaicism in human somatic and embryonic stem cell populations
De novocopy number variations are known to occur in somatic cell populations and pluripotent stem cells. Here the authors use single-cell array comparative genomic hybridization to identify copy number variations in individual human somatic and embryonic stem cells.
- Kurt Jacobs
- , Afroditi Mertzanidou
- & Claudia Spits
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| Open AccessClonal culturing of human embryonic stem cells on laminin-521/E-cadherin matrix in defined and xeno-free environment
Laminin-511 and its cell-binding domain support long-term self-renewal of human pluripotent stem cells in xeno-free culture conditions. Here the authors show that a xeno-free culture matrix consisting of a full-length laminin-521 and the cell–cell adhesion protein E-cadherin supports clonal expansion of human embryonic stem cells.
- Sergey Rodin
- , Liselotte Antonsson
- & Karl Tryggvason
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Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment
Factors inducing epithelial to mesenchymal transition, such as the transcriptional repressor Snail1, have been implicated in cancer stem cell development and function. Here Lin et al.report that endogenous Snail1 is not required for embryonic stem cell pluripotency and self-renewal, but rather regulates Wnt-induced epiblast differentiation.
- Yongshun Lin
- , Xiao-Yan Li
- & Stephen J. Weiss
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Gene regulation and priming by topoisomerase IIα in embryonic stem cells
Topoisomerase 2α (Top2α) has essential roles during DNA replication, whereas its isoform Top2β is implicated in gene expression. Thakurela et al.show that Top2α is also required for stem-cell transcriptome regulation and primes developmental genes for activation by Top2β upon terminal differentiation.
- Sudhir Thakurela
- , Angela Garding
- & Vijay K. Tiwari
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Modulation of β-catenin function maintains mouse epiblast stem cell and human embryonic stem cell self-renewal
Wnt/β-catenin signalling can regulate both self-renewal and differentiation of pluripotent stem cells. Here Kim et al.show that transcriptional regulation by nuclear β-catenin induces the differentiation of mouse epiblast stem cells and human embryonic stem cells, whereas cytoplasmic β-catenin supports their self-renewal.
- Hoon Kim
- , Jun Wu
- & Qi-Long Ying
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Article
| Open AccesshESC-derived Olig2+ progenitors generate a subtype of astroglia with protective effects against ischaemic brain injury
Astroglia are heterogeneous in phenotype and not all astrocytes are equivalent in their ability to repair injured brain. Here, the authors show that two defined subtypes of astroglia generated from hESC-derived Olig2-positive versus Olig2-negative neural progenitors, exhibit distinct properties and neuroprotective effects.
- Peng Jiang
- , Chen Chen
- & Wenbin Deng
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Zscan4 restores the developmental potency of embryonic stem cells
Mouse embryonic stem cells gradually lose their developmental potency in long-term culture. Here the authors show that their deteriorating developmental potency can be restored by transient activation of the Zscan4gene.
- Tomokazu Amano
- , Tetsuya Hirata
- & Minoru S. H. Ko
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Max is a repressor of germ cell-related gene expression in mouse embryonic stem cells
Even though both embryonic stem cells and primordial germ cells express pluripotency markers, they differ in their developmental potential. Maeda et al. show that, in embryonic stem cells, the Myc family member Max mediates epigenetic repression of genes involved in germ cell development.
- Ikuma Maeda
- , Daiji Okamura
- & Yasuhisa Matsui
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| Open AccessA thermoresponsive and chemically defined hydrogel for long-term culture of human embryonic stem cells
To transfer cultured human embryonic stem cells (hESCs) between culture dishes, cells need to be released using mechanical, enzymatic or chemical means, which can damage cells. Zhanget al. describe a thermomodulatable hydrogel that allows gentle, reagent-free cell passaging for the long-term culture of hESCs.
- Rong Zhang
- , Heidi K. Mjoseng
- & Mark Bradley
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The RB family is required for the self-renewal and survival of human embryonic stem cells
While human embryonic stem cells (ESC) hold great therapeutic promise, many aspects of their basic biology remain poorly understood. Conklin et al.show that too much or too little activation of RB family proteins is detrimental to human ESC populations and identify unique cell cycle regulatory networks in these cells.
- Jamie F. Conklin
- , Julie Baker
- & Julien Sage
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| Open AccessEndogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors
Human embryonic stem cell cultures are morphologically heterogeneous. Here, differences in Wnt signalling are shown to contribute to this heterogeneity, cells containing high levels of Wnt form endodermal and cardiac cells, whereas cells with low Wnt form neuroectodermal cells, when differentiation is induced.
- Timothy A. Blauwkamp
- , Shelly Nigam
- & Roel Nusse
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Histone modifications and lamin A regulate chromatin protein dynamics in early embryonic stem cell differentiation
Chromatin in embryonic stem cells is present in an open state presumably to facilitate gene expression changes required for pluripotency and subsequent multilineage differentiation. This study describes roles for lamin A, histone acetylation and G9a-mediated histone H3 lysine 9 methylation in regulating chromatin plasticity in these cells.
- Shai Melcer
- , Hadas Hezroni
- & Eran Meshorer
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Reprogramming within hours following nuclear transfer into mouse but not human zygotes
The generation of human cell lines using somatic cell nuclear transfer has been difficult to achieve. In this study, Egliet al. show that while mouse eggs reprogram somatic cells within hours, human eggs arrest after nuclear transfer which may be due to a lack of genome transcription.
- Dieter Egli
- , Alice E. Chen
- & Kevin Eggan
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| Open AccessRetinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state
There is much interest in generating motor neurons from embryonic stem cells because they may be useful for the study of neurodegenerative disease. Pataniet al. show that in the absence of retinoic acid, neurons with features of medial motor columnar neurons can be generated from human embryonic stem cells.
- R. Patani
- , A. J. Hollins
- & S. Chandran
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An optimized small molecule inhibitor cocktail supports long-term maintenance of human embryonic stem cells
Stem cell-mediated regenerative medicine requires the development of defined culture systems for the maintenance of human embryonic stem cells. Here, feedback system control is used to identify a combination of three small molecule inhibitors that enables long-term human embryonic stem cell maintenance.
- Hideaki Tsutsui
- , Bahram Valamehr
- & Hong Wu