Phenotyping Neurodegeneration in Human iPSCs

Abstract

Induced pluripotent stem cell (iPSC) technology holds promise for modeling neurodegenerative diseases. Traditional approaches for disease modeling using animal and cellular models require knowledge of disease mutations. However, many patients with neurodegenerative diseases do not have a known genetic cause. iPSCs offer a way to generate patient-specific models and study pathways of dysfunction in an in vitro setting in order to understand the causes and subtypes of neurodegeneration. Furthermore, iPSC-based models can be used to search for candidate therapeutics using high-throughput screening. Here we review how iPSC-based models are currently being used to further our understanding of neurodegenerative diseases, as well as discuss their challenges and future directions. Expected final online publication date for the Annual Review of Biomedical Data Science, Volume 4 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

ErbB2pY‐1248 as a predictive biomarker for Parkinson's disease based on research with RPPA technology and in vivo verification

“…Future studies are necessary to be performed to validate the sensitivity and specificity of ErbB2 pY‐1248 as a PD biomarker and confirm its high correlation with disease development and progression. IPSCs technology is a promising tool to support the clinical application of ErbB2 pY‐1248 , which can efficiently generate iPSCs from readily available tissues, differentiating into CNS‐specific cells 94–96 . Long‐term survival and function of dopaminergic neurons derived from autologous human iPSCs have been reported in non‐human primate models of PD 97,98 .…”

“…IPSCs technology is a promising tool to support the clinical application of ErbB2 pY‐1248 , which can efficiently generate iPSCs from readily available tissues, differentiating into CNS‐specific cells. 94 , 95 , 96 Long‐term survival and function of dopaminergic neurons derived from autologous human iPSCs have been reported in non‐human primate models of PD. 97 , 98 In the future, iPSCs might be applied to PD diagnosis by using ErbB2 pY‐1248 as a PD biomarker.…”

Recent Advances in High-Content Imaging and Analysis in iPSC-Based Modelling of Neurodegenerative Diseases

“…Nowadays, phenotypic analysis of human iPSC (hiPSC)-based disease models is the most reliable probe (i) to define cellular differences and vulnerabilities in patients compared to healthy control cells, as well as (ii) to investigate the underlying molecular mechanisms of various neurodegenerative processes [56,[66][67][68]. Cell body shrinkage, axonal degeneration, and/or neurite pathologies are key pathological hallmarks in a number of neurodegenerative diseases, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and hereditary spastic paraplegia (HSP) [14,40].…”

Mitochondrial dysfunction of induced pluripotent stem cells-based neurodegenerative disease modeling and therapeutic strategy

“…Induced pluripotent stem cells (iPSCs) are pluripotent, which indicates their capacity to differentiate into almost all human cell types with identical genetic background of the donor patient ( Li and Fraenkel, 2021 ). This process provides developmental cues to areas of interest.…”