scholarly journals Induced Pluripotent Stem Cell Neuronal Models for the Study of Autophagy Pathways in Human Neurodegenerative Disease

Cells ◽  
2017 ◽  
Vol 6 (3) ◽  
pp. 24 ◽  
Author(s):  
Natalia Jiménez-Moreno ◽  
Petros Stathakos ◽  
Maeve Caldwell ◽  
Jon Lane
Keyword(s):  
Stem Cell ◽  
Neurodegenerative Disease ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Induced Pluripotent ◽  
Human Neurodegenerative Disease

scholarly journals Reduction of HDAC2 expression in human induced pluripotent stem cell derived neurons improves neuronal maturation, mitochondrial dynamics and cellular neurodegenerative disease phenotypes

2021 ◽  
Author(s):  
Harald Frankowski ◽  
Fred Yeboah ◽  
Bonnie J. Berry ◽  
Chizuru Kinoshita ◽  
Michelle Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neurodegenerative Disease ◽  
Pluripotent Stem Cell ◽  
Mitochondrial Dynamics ◽  
Induced Pluripotent Stem Cell ◽  
Adult Brain ◽  
Aberrant Expression ◽  
Histone Deacetylase 2 ◽  
Knock Down ◽  
Induced Pluripotent

AbstractHistone deacetylase 2 (HDAC2) is a major HDAC protein in the adult brain and has been shown to regulate many neuronal genes. Aberrant expression of HDAC2 and subsequent dysregulation of neuronal gene expression is implicated in neurodegeneration and brain aging. Human induced pluripotent stem cell-derived neurons (hiPSC-Ns) are widely used models for studying neurodegenerative disease mechanisms, but the role of HDAC2 in hiPSC-N differentiation and maturation has not been explored. In this study, we show that levels of HDAC2 progressively decrease as hiPSCs are differentiated towards neurons. This suppression of HDAC2 inversely corresponds to an increase in neuron-specific isoforms of Endophilin-B1, a multifunctional protein involved in mitochondrial dynamics. Expression of neuron-specific isoforms of Endophilin-B1 is accompanied by concomitant expression of a neuron-specific alternative splicing factor, SRRM4. Manipulation of HDAC2 and Endophilin-B1 using lentiviral approaches shows that knock-down of HDAC2 or overexpression of a neuron-specific Endophilin-B1 isoform promotes mitochondrial elongation and protects against cytotoxic stress in hiPSC-Ns, while HDAC2 knock-down specifically influences genes regulating mitochondrial dynamics and synaptogenesis. Furthermore, HDAC2 knock-down promotes enhanced mitochondrial respiration and reduces levels of neurotoxic amyloid beta peptides. Collectively, our study demonstrates a role for HDAC2 in hiPSC-neuronal differentiation, highlights neuron-specific isoforms of Endophilin-B1 as a marker of differentiating hiPSC-Ns, and demonstrates that HDAC2 regulates key neuronal and mitochondrial pathways in hiPSC-Ns.

scholarly journals Mechanistic and Translational Advances Using iPSC-Derived Blood Cells

2020 ◽  
Author(s):  
Christopher S. Thom ◽  
Stella T. Chou ◽  
Deborah L. French
Keyword(s):  
Stem Cell ◽  
Neurodegenerative Disease ◽  
Blood Cells ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Lymphoid Cells ◽  
Model Systems ◽  
Hematologic Disorders ◽  
Hematopoietic Disorders ◽  
Induced Pluripotent

Human induced pluripotent stem cell (iPSC)-based model systems can be used to produce blood cells for the study of both hematologic and non-hematologic disorders. This commentary discusses recent advances that have utilized iPSC-derived red blood cells, megakaryocytes, myeloid cells, and lymphoid cells to model hematopoietic disorders. In addition, we review recent studies that have defined how microglial cells differentiated from iPSC-derived monocytes impact neurodegenerative disease. Related translational insights highlight the utility of iPSC models for studying pathologic anemia, bleeding, thrombosis, autoimmunity, immunodeficiency, blood cancers, and neurodegenerative disease such as Alzheimer’s.

Use of 3D culture systems to generate human induced pluripotent stem cell-derived [beta]-cells in vitro

2018 ◽  
Author(s):  
Fantuzzi Federica ◽  
Toivonen Sanna ◽  
Schiavo Andrea Alex ◽  
Pachera Nathalie ◽  
Rajaei Bahareh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Beta Cells ◽  
Pluripotent Stem Cell ◽  
3D Culture ◽  
Induced Pluripotent Stem Cell ◽  
Culture Systems ◽  
Induced Pluripotent
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