scholarly journals Enhanced maturation of human stem cell derived interneurons by mTOR activation

2019 ◽  
Author(s):  
Jianhua Chu ◽  
Megan L. Fitzgerald ◽  
Neha Sehgal ◽  
William Manley ◽  
Shane Fitzgerald ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mtor Inhibitor ◽  
Directed Differentiation ◽  
Human Stem Cell ◽  
Cortical Interneuron ◽  
Novel Approach ◽  
Human Neurons ◽  
Cell Recording ◽  
Rat Neocortex ◽  
Line Following

SummaryThe use of stem cell derived neurons for cell-based therapies is limited by a protracted maturation. We present a novel approach for accelerating the post-mitotic maturation of human stem cell derived interneurons via the activation of mTOR signaling. Lox sites were placed within PTEN, a key mTOR inhibitor, in a cortical interneuron (CIn) reporter line. Following directed differentiation and purification by FACS, the CIns were exposed to Cre-expressing lentivirus, then transplanted into mouse neocortex or plated onto cultured rat neocortex. Input synaptogenesis and dendritogenesis was greatly enhanced in the PTEN-deleted CIns. Whole-cell recording of the PTEN-deleted CIns in slices of transplanted neocortex revealed multiple indices of enhanced maturation. Finally, we observed similar effects using transient, doxycycline-inducible activation of AKT. We thus present an inducible, reversible approach for accelerating the maturation of human stem cell derived CIns, and to study the influences of this disease-related signaling system in human neurons.

Human stem cell models of neurodegeneration: a novel approach to study mechanisms of disease development

2013 ◽  
Vol 127 (2) ◽  
pp. 151-173 ◽  
Author(s):  
Gunnar Hargus ◽  
Marc Ehrlich ◽  
Anna-Lena Hallmann ◽  
Tanja Kuhlmann
Keyword(s):  
Stem Cell ◽  
Disease Development ◽  
Human Stem Cell ◽  
Cell Models ◽  
Novel Approach ◽  
Stem Cell Models

scholarly journals Modelling Lyssavirus Infections in Human Stem Cell-Derived Neural Cultures

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 359 ◽  
Author(s):  
Vinod Sundaramoorthy ◽  
Nathan Godde ◽  
Ryan J. Farr ◽  
Diane Green ◽  
John M. Haynes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Human Life ◽  
Model System ◽  
Human Rabies ◽  
Human Stem Cell ◽  
Human Neurons ◽  
Neural Cultures ◽  
Rabies Pathogenesis

Rabies is a zoonotic neurological infection caused by lyssavirus that continues to result in devastating loss of human life. Many aspects of rabies pathogenesis in human neurons are not well understood. Lack of appropriate ex-vivo models for studying rabies infection in human neurons has contributed to this knowledge gap. In this study, we utilize advances in stem cell technology to characterize rabies infection in human stem cell-derived neurons. We show key cellular features of rabies infection in our human neural cultures, including upregulation of inflammatory chemokines, lack of neuronal apoptosis, and axonal transmission of viruses in neuronal networks. In addition, we highlight specific differences in cellular pathogenesis between laboratory-adapted and field strain lyssavirus. This study therefore defines the first stem cell-derived ex-vivo model system to study rabies pathogenesis in human neurons. This new model system demonstrates the potential for enabling an increased understanding of molecular mechanisms in human rabies, which could lead to improved control methods.

scholarly journals CRISPR/Cas9 Gene editing of RyR2 in human stem cell-derived cardiomyocytes provides a novel approach in investigating dysfunctional Ca2+ signaling

Cell Calcium ◽  
2018 ◽  
Vol 73 ◽  
pp. 104-111 ◽  
Author(s):  
Hua Wei ◽  
Xiao-Hua Zhang ◽  
Cassandra Clift ◽  
Naohiro Yamaguchi ◽  
Martin Morad
Keyword(s):  
Stem Cell ◽  
Gene Editing ◽  
Human Stem Cell ◽  
Novel Approach
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