Cell Stem Cell (CELL STEM CELL)

Publications in this journal

• Article: Forebrain Engraftment by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice

  Xiaoning Han, Michael Chen, Fushun Wang, Martha Windrem, Su Wang, Steven Shanz, Qiwu Xu, Nancy Ann Oberheim, Lane Bekar, Sarah Betstadt, Alcino J. Silva, Takahiro Takano, Steven A. Goldman, Maiken Nedergaard
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  ABSTRACT: Human astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution. To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. The engrafted human glia were gap-junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca2+ signals 3-fold faster than their hosts. Long-term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning. Mice allografted with murine GPCs showed no enhancement of either LTP or learning. These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice.
  Cell Stem Cell 03/2013; 12(3):342-353.
• Article: Forebrain Engraftment by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice

  Xiaoning Han, Michael Chen, Fushun Wang, Martha Windrem, Su Wang, Steven Shanz, Qiwu Xu, Nancy Ann Oberheim, Lane Bekar, Sarah Betstadt, Alcino J. Silva, Takahiro Takano, Steven A. Goldman, Maiken Nedergaard
  [show abstract] [hide abstract]
  ABSTRACT: Human astrocytes are larger and more complex than those of infraprimate mammals, suggesting that their role in neural processing has expanded with evolution. To assess the cell-autonomous and species-selective properties of human glia, we engrafted human glial progenitor cells (GPCs) into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. The engrafted human glia were gap-junction-coupled to host astroglia, yet retained the size and pleomorphism of hominid astroglia, and propagated Ca2+ signals 3-fold faster than their hosts. Long-term potentiation (LTP) was sharply enhanced in the human glial chimeric mice, as was their learning, as assessed by Barnes maze navigation, object-location memory, and both contextual and tone fear conditioning. Mice allografted with murine GPCs showed no enhancement of either LTP or learning. These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice.
  Cell Stem Cell 03/2013; 12(3):342-353.
• Article: The transcriptional landscape of hematopoietic stem cell ontogeny

  McKinney-Freeman S, Cahan P, Li H, Lacadie SA, Huang HT, Curran M, Loewer S, Naveiras O, Kathrein KL, Konantz M, Lengerke C, Zon LI, Collins JJ, Daley GQ
  Cell Stem Cell 01/2012;
• Article: Adult Human RPE Can Be Activated into a Multipotent Stem Cell that Produces Mesenchymal Derivatives

  Enrique Salero, Timothy A. Blenkinsop, Barbara Corneo, Ashley Harris, David Rabin, Jeffrey H. Stern, Sally Temple
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  ABSTRACT: The retinal pigment epithelium (RPE) is a monolayer of cells underlying and supporting the neural retina. It begins as a plastic tissue, capable, in some species, of generating lens and retina, but differentiates early in development and remains normally nonproliferative throughout life. Here we show that a subpopulation of adult human RPE cells can be activated in vitro to a self-renewing cell, the retinal pigment epithelial stem cell (RPESC) that loses RPE markers, proliferates extensively, and can redifferentiate into stable cobblestone RPE monolayers. Clonal studies demonstrate that RPESCs are multipotent and in defined conditions can generate both neural and mesenchymal progeny. This plasticity may explain human pathologies in which mesenchymal fates are seen in the eye, for example in proliferative vitroretinopathy (PVR) and phthisis bulbi. This study establishes the RPESC as an accessible, human CNS-derived multipotent stem cell, useful for the study of fate choice, replacement therapy, and disease modeling.
  Cell Stem Cell 01/2012; 10:88-95.
• Article: Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy

  Marteyn A, Maury Y, Gauthier MM, Lecuyer C, Vernet R, Denis J, Pietu G, Peschanski M, Martinat C
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  ABSTRACT: Myotonic dystrophy type 1 (DM1) is a multisystem disorder affecting a variety of organs, including the central nervous system. By using neuronal progeny derived from human embryonic stem cells carrying the causal DM1 mutation, we have identified an early developmental defect in genes involved in neurite formation and the establishment of neuromuscular connections. Differential gene expression profiling and quantitative RT-PCR revealed decreased expression of two members of the SLITRK family in DM1 neural cells and in DM1 brain biopsies. In addition, DM1 motoneuron/muscle cell cocultures showed alterations that are consistent with the known role of SLITRK genes in neurite outgrowth, neuritogenesis, and synaptogenesis. Rescue and knockdown experiments suggested that the functional defects can be directly attributed to SLITRK misexpression. These neuropathological mechanisms may be clinically significant for the functional changes in neuromuscular connections associated with DM1.
  Cell Stem Cell 04/2011;
• Article: Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling.

  Ferron SR, Pozo N, Laguna A, Aranda S, Moreno Estelles M, Fillat C, de la Luna S, Sánchez P, Arbonés ML, Fariñas I
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  ABSTRACT: Stem cell division can result in two sibling cells exhibiting differential mitogenic and self-renewing potential. Here, we present evidence that the dual-specificity kinase Dyrk1A is part of a molecular pathway involved in the regulation of biased epidermal growth factor receptor (EGFR) signaling in the progeny of dividing neural stem cells (NSC) of the adult subependymal zone (SEZ). We show that EGFR asymmetry requires regulated sorting and that a normal Dyrk1a dosage is required to sustain EGFR in the two daughters of a symmetrically dividing progenitor. Dyrk1A is symmetrically or asymmetrically distributed during mitosis, and biochemical analyses indicate that it prevents endocytosis-mediated degradation of EGFR by a mechanism that requires phosphorylation of the EGFR signaling modulator Sprouty2. Finally, Dyrk1a heterozygous NSCs exhibit defects in self-renewal, EGF-dependent cell-fate decisions, and long-term persistence in vivo, suggesting that symmetrical divisions play a role in the maintenance of the SEZ reservoir
  Cell Stem Cell 09/2010; 7((3)):367-79.
• Article: One flew over the progenitor's nest: migratory cells find a home in osteoarthritic cartilage.

  Khan IM, Williams R, Archer CW
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  ABSTRACT: Articular cartilage is the target tissue of osteoarthritis (OA), a degenerative disease with no cure. In this issue of Cell Stem Cell, Miosge and colleagues (Koelling et al., 2009) report that migratory progenitor cells occupy degenerating OA tissue but that this population is not present in healthy cartilage.
  Cell Stem Cell 04/2009; 4(3;4):282-4.
• Article: Response to Letter from Löser et al.

  Aaron D Levine
  Cell Stem Cell 09/2008; 3(2):131.
• Article: The epigenetics of fragile X syndrome.

  Stephen T Warren
  Cell Stem Cell 12/2007; 1(5):488-9.
• Article: Neurotrophin receptor-mediated death of misspecified neurons generated from embryonic stem cells lacking Pax6.

  Vassiliki Nikoletopoulou, Nicolas Plachta, Nicolas D Allen, Luisa Pinto, Magdalena Götz, Yves-Alain Barde
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  ABSTRACT: Pax6-positive radial glial (RG) cells are the progenitors of most glutamatergic neurons in the cortex, a lineage that can be recapitulated in vitro using embryonic stem (ES) cells. We show here that ES cells lacking Pax6, a transcription factor long known to be essential for cortical development, generate Mash1-positive RG cells that differentiate in GABAergic neurons. These neurons express high levels of the neurotrophin receptor p75NTR causing their rapid death. Pax6 function was also investigated following transplantation of ES cells in the developing chick telencephalon and in mice lacking both Pax6 and p75NTR. Taken together, our results indicate that reliable predictions can be made with cultured ES cells when used to explore the role of genes impacting early aspects of mammalian neurogenesis. They also provide a novel opportunity to compare the molecular constituents of glutamatergic with those of GABA-ergic neurons and to explore the mechanisms of their generation.
  Cell Stem Cell 12/2007; 1(5):529-40.
• Article: The generation of six clinical-grade human embryonic stem cell lines.

  Jeremy Micah Crook, Teija Tuulikki Peura, Lucy Kravets, Alexis Gina Bosman, Jeremy James Buzzard, Rachel Horne, Hannes Hentze, Norris Ray Dunn, Robert Zweigerdt, Florence Chua, Alan Upshall, Alan Colman
  Cell Stem Cell 12/2007; 1(5):490-4.