Glycogen Synthase Kinase-3 Inhibition Promotes Proliferation and Neuronal Differentiation of Human-Induced Pluripotent Stem Cell-Derived Neural Progenitors

2012 ◽  
Vol 21 (17) ◽  
pp. 3233-3243 ◽  
Author(s):  
Fereshteh Esfandiari ◽  
Ali Fathi ◽  
Hamid Gourabi ◽  
Sahar Kiani ◽  
Shiva Nemati ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neuronal Differentiation ◽  
Pluripotent Stem Cell ◽  
Glycogen Synthase ◽  
Induced Pluripotent Stem Cell ◽  
Neural Progenitors ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Induced Pluripotent

scholarly journals Activation of Neurogenesis in Multipotent Stem Cells Cultured In Vitro and in the Spinal Cord Tissue After Severe Injury by Inhibition of Glycogen Synthase Kinase-3

2020 ◽  
Author(s):  
Francisco Javier Rodriguez-Jimenez ◽  
Angel Vilches ◽  
Maria Amparo Perez-Arago ◽  
Eleonora Clemente ◽  
Raquel Roman ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cell ◽  
Motor Function ◽  
Pluripotent Stem Cell ◽  
Glycogen Synthase ◽  
Neural Progenitors ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Spinal Cord Tissue

Abstract The inhibition of glycogen synthase kinase-3 (GSK-3) can induce neurogenesis, and the associated activation of Wnt/β-catenin signaling via GSK-3 inhibition may represent a means to promote motor function recovery following spinal cord injury (SCI) via increased astrocyte migration, reduced astrocyte apoptosis, and enhanced axonal growth. Herein, we assessed the effects of GSK-3 inhibition in vitro on the neurogenesis of ependymal stem/progenitor cells (epSPCs) resident in the mouse spinal cord and of human embryonic stem cell–derived neural progenitors (hESC-NPs) and human-induced pluripotent stem cell–derived neural progenitors (hiPSC-NPs) and in vivo on spinal cord tissue regeneration and motor activity after SCI. We report that the treatment of epSPCs and human pluripotent stem cell–derived neural progenitors (hPSC-NPs) with the GSK-3 inhibitor Ro3303544 activates β-catenin signaling and increases the expression of the bIII-tubulin neuronal marker; furthermore, the differentiation of Ro3303544-treated cells prompted an increase in the number of terminally differentiated neurons. Administration of a water-soluble, bioavailable form of this GSK-3 inhibitor (Ro3303544-Cl) in a severe SCI mouse model revealed the increased expression of bIII-tubulin in the injury epicenter. Treatment with Ro3303544-Cl increased survival of mature neuron types from the propriospinal tract (vGlut1, Parv) and raphe tract (5-HT), protein kinase C gamma–positive neurons, and GABAergic interneurons (GAD65/67) above the injury epicenter. Moreover, we observed higher numbers of newly born BrdU/DCX-positive neurons in Ro3303544-Cl–treated animal tissues, a reduced area delimited by astrocyte scar borders, and improved motor function. Based on this study, we believe that treating animals with epSPCs or hPSC-NPs in combination with Ro3303544-Cl deserves further investigation towards the development of a possible therapeutic strategy for SCI.

Lithium chloride improves the efficiency of induced pluripotent stem cell-derived neurospheres

2015 ◽  
Vol 396 (8) ◽  
pp. 923-928 ◽  
Author(s):  
Azita Parvaneh Tafreshi ◽  
Aude Sylvain ◽  
Guizhi Sun ◽  
Daniella Herszfeld ◽  
Keith Schulze ◽  
...  
Keyword(s):  
Stem Cell ◽  
Lithium Chloride ◽  
Pluripotent Stem Cell ◽  
Lithium Treatment ◽  
Formation Rate ◽  
Induced Pluripotent Stem Cell ◽  
Neural Progenitors ◽  
Neural Cells ◽  
Proliferating Cells ◽  
Induced Pluripotent

Abstract Induced pluripotent stem cell (iPSC)-derived neurospheres, which consist mainly of neural progenitors, are considered to be a good source of neural cells for transplantation in regenerative medicine. In this study, we have used lithium chloride, which is known to be a neuroprotective agent, in an iPSC-derived neurosphere model, and examined both the formation rate and size of the neurospheres as well as the proliferative and apoptotic status of their contents. Our results showed that lithium enhanced the formation and the sizes of the iPSC-derived neurospheres, increased the number of Ki67-positive proliferating cells, but reduced the number of the TUNEL-positive apoptotic cells. This increased number of Ki67 proliferating cells was secondary to the decreased apoptosis and not to the stimulation of cell cycle entry, as the expression of the proliferation marker cyclin D1 mRNA did not change after lithium treatment. Altogether, we suggest that lithium enhances the survival of neural progenitors and thus the quality of the iPSC-derived neurospheres, which may strengthen the prospect of using lithium-treated pluripotent cells and their derivatives in a clinical setting.

scholarly journals Characterization of DNA Methylomic Signatures in Induced Pluripotent Stem Cells During Neuronal Differentiation

2021 ◽  
Vol 9 ◽  
Author(s):  
Jennifer Imm ◽  
Ehsan Pishva ◽  
Muhammadd Ali ◽  
Talitha L. Kerrigan ◽  
Aaron Jeffries ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cell ◽  
Neuronal Differentiation ◽  
Pluripotent Stem Cell ◽  
Interaction Network ◽  
Induced Pluripotent Stem Cell ◽  
Gene Interaction ◽  
Gene Interaction Network ◽  
Induced Pluripotent

In development, differentiation from a pluripotent state results in global epigenetic changes, although the extent to which this occurs in induced pluripotent stem cell-based neuronal models has not been extensively characterized. In the present study, induced pluripotent stem cell colonies (33Qn1 line) were differentiated and collected at four time-points, with DNA methylation assessed using the Illumina Infinium Human Methylation EPIC BeadChip array. Dynamic changes in DNA methylation occurring during differentiation were investigated using a data-driven trajectory inference method. We identified a large number of Bonferroni-significant loci that showed progressive alterations in DNA methylation during neuronal differentiation. A gene–gene interaction network analysis identified 60 densely connected genes that were influential in the differentiation of neurons, with STAT3 being the gene with the highest connectivity.

scholarly journals Functional changes of AMPA responses in human induced pluripotent stem cell–derived neural progenitors in fragile X syndrome

2018 ◽  
Vol 11 (513) ◽  
pp. eaan8784 ◽  
Author(s):  
Venkat Swaroop Achuta ◽  
Tommi Möykkynen ◽  
Ulla-Kaisa Peteri ◽  
Giorgio Turconi ◽  
Claudio Rivera ◽  
...  
Keyword(s):  
Stem Cell ◽  
Fragile X Syndrome ◽  
Pluripotent Stem Cell ◽  
Fragile X ◽  
Induced Pluripotent Stem Cell ◽  
Neural Progenitors ◽  
Functional Changes ◽  
Induced Pluripotent
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