scholarly journals Glycogen synthase kinase 3 induces multilineage maturation of human pluripotent stem cell-derived lung progenitors in 3D culture

Development ◽  
2018 ◽  
Vol 146 (2) ◽  
pp. dev171652 ◽  
Author(s):  
Ana Luisa Rodrigues Toste de Carvalho ◽  
Alexandros Strikoudis ◽  
Hsiao-Yun Liu ◽  
Ya-Wen Chen ◽  
Tiago J. Dantas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Glycogen Synthase ◽  
3D Culture ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Human Pluripotent Stem Cell ◽  
Lung Progenitors

scholarly journals Glycogen Synthase Kinase 3 induces multilineage maturation of human pluripotent stem cell-derived lung progenitors in 3D culture

2018 ◽  
Author(s):  
Ana Luisa Rodrigues Toste de Carvalho ◽  
Alexandros Strikoudis ◽  
Tiago J. Dantas ◽  
Ya-Wen Chen ◽  
Hsiao-Yun Liu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Lung Development ◽  
Human Lung ◽  
Glycogen Synthase ◽  
3D Culture ◽  
Alveolar Epithelial Cells ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Type I ◽  
Lung Progenitors

Although strategies for directed differentiation of human pluripotent stem cells (hPSCs) into lung and airway have been established, terminal maturation of the cells remains a vexing problem. We show here that in Collagen I 3D cultures in the absence of glycogen synthase kinase 3 (GSK3) inhibition, hPSC-derived lung progenitors (LPs) undergo multilineage maturation into proximal cells arranged in pseudostratified epithelia, type I alveolar epithelial cells and morphologically mature type II cells. Enhanced cell cycling, one of the signaling outputs of GSK3 inhibition, plays a role in the maturation-inhibiting effect of GSK3 inhibition. Using this model, we show NOTCH signaling induced a distal at the expense of a proximal and ciliated cell fate, while WNT signaling promoted a proximal, club cell fate, thus implicating both signaling pathways in proximodistal specification in human lung development. These findings establish an approach to achieve multilineage maturation of lung and airway cells from hPSCs, demonstrate a pivotal role of GSK3 in the maturation of lung progenitors, and provide novel insight into proximodistal specification during human lung development.

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.

scholarly journals A Genome-wide Analysis of Human Pluripotent Stem Cell-Derived Endothelial Cells in 2D or 3D Culture

2017 ◽  
Vol 8 (4) ◽  
pp. 907-918 ◽  
Author(s):  
Jue Zhang ◽  
Michael P. Schwartz ◽  
Zhonggang Hou ◽  
Yongsheng Bai ◽  
Hamisha Ardalani ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
3D Culture ◽  
Human Pluripotent Stem Cell ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome

Glycogen synthase kinase-3 is an in vivo regulator of hematopoietic stem cell repopulation

2005 ◽  
Vol 12 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Jennifer J Trowbridge ◽  
Anargyros Xenocostas ◽  
Randall T Moon ◽  
Mickie Bhatia
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Hematopoietic Stem ◽  
Cell Repopulation
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