scholarly journals Ngn2 induces diverse neuronal lineages from human pluripotency

2020 ◽  
Author(s):  
Hsiu-Chuan Lin ◽  
Zhisong He ◽  
Sebastian Ebert ◽  
Maria Schörnig ◽  
Malgorzata Santel ◽  
...  
Keyword(s):  
Nervous System ◽  
Pluripotent Stem Cells ◽  
Time Course ◽  
Neurological Diseases ◽  
Molecular Heterogeneity ◽  
Neuron Type ◽  
Functional Maturation ◽  
Human Neurons ◽  
Induced Pluripotent ◽  
Two Populations

Human neurons engineered from induced pluripotent stem cells (iPSCs) through Neurogenin 2 (Ngn2) overexpression are widely used to study neuronal differentiation mechanisms and to model neurological diseases. However, the differentiation paths and heterogeneity of emerged neurons have not been fully explored. Here we used single-cell transcriptomics to dissect the cell states that emerge during Ngn2 overexpression across a time course from pluripotency to neuron functional maturation. We find a substantial molecular heterogeneity in the neuron types generated, with at least two populations that express genes associated with neurons of the peripheral nervous system. Neuron heterogeneity is observed across multiple iPSC clones and lines from different individuals. We find that neuron fate acquisition is sensitive to Ngn2 expression level and the duration of Ngn2 forced expression. Our data reveals that Ngn2 dosage can regulate neuron fate acquisition, and that Ngn2-iN heterogeneity can confound results that are sensitive to neuron type.

scholarly journals Identification of Molecular Signatures in Neural Differentiation and Neurological Diseases Using Digital Color-Coded Molecular Barcoding

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Debora Salerno ◽  
Alessandro Rosa
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Neural Differentiation ◽  
Disease Modeling ◽  
Neurological Diseases ◽  
Embryonic Stem ◽  
Molecular Signatures ◽  
Molecular Barcoding ◽  
Induced Pluripotent

Human pluripotent stem cells (PSCs), including embryonic stem cells and induced pluripotent stem cells, represent powerful tools for disease modeling and for therapeutic applications. PSCs are particularly useful for the study of development and diseases of the nervous system. However, generating in vitro models that recapitulate the architecture and the full variety of subtypes of cells that make the complexity of our brain remains a challenge. In order to fully exploit the potential of PSCs, advanced methods that facilitate the identification of molecular signatures in neural differentiation and neurological diseases are highly demanded. Here, we review the literature on the development and application of digital color-coded molecular barcoding as a potential tool for standardizing PSC research and applications in neuroscience. We will also describe relevant examples of the use of this technique for the characterization of the heterogeneous composition of the brain tumor glioblastoma multiforme.

scholarly journals Establishment and characterization of induced pluripotent stem cells (iPSCs) from central nervous system lupus erythematosus

2019 ◽  
Vol 23 (11) ◽  
pp. 7382-7394 ◽  
Author(s):  
Maria Teresa De Angelis ◽  
Gianluca Santamaria ◽  
Elvira Immacolata Parrotta ◽  
Stefania Scalise ◽  
Michela Lo Conte ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Induced Pluripotent Stem Cells ◽  
Lupus Erythematosus ◽  
Pluripotent Stem Cells ◽  
Central Nervous System Lupus ◽  
Induced Pluripotent

scholarly journals From “Directed Differentiation” to “Neuronal Induction”: Modeling Neuropsychiatric Disease

2015 ◽  
Vol 10s1 ◽  
pp. BMI.S20066 ◽  
Author(s):  
Seok-Man Ho ◽  
Aaron Topol ◽  
Kristen J. Brennand
Keyword(s):  
Psychiatric Disorders ◽  
Neurological Diseases ◽  
Disease Onset ◽  
Induced Pluripotent Stem Cell ◽  
Directed Differentiation ◽  
Neuropsychiatric Disease ◽  
Somatic Cell Reprogramming ◽  
Human Neurons ◽  
Induced Pluripotent

Aberrant behavior and function of neurons are believed to be the primary causes of most neurological diseases and psychiatric disorders. Human postmortem samples have limited availability and, while they provide clues to the state of the brain after a prolonged illness, they offer limited insight into the factors contributing to disease onset. Conversely, animal models cannot recapitulate the polygenic origins of neuropsychiatric disease. Novel methods, such as somatic cell reprogramming, deliver nearly limitless numbers of pathogenic human neurons for the study of the mechanism of neuropsychiatric disease initiation and progression. First, this article reviews the advent of human induced pluripotent stem cell (hiPSC) technology and introduces two major methods, “directed differentiation” and “neuronal induction,” by which it is now possible to generate neurons for modeling neuropsychiatric disease. Second, it discusses the recent applications, and the limitations, of these technologies to in vitro studies of psychiatric disorders.

scholarly journals ApoE4-carrying Human Astrocytes Oversupply Cholesterol into Neurons and Promote Aβ Generation

2020 ◽  
Author(s):  
Se-In Lee ◽  
Woojin Jeong ◽  
Sukhee Cho ◽  
Hyein Lee ◽  
Yonghee Jang ◽  
...  
Keyword(s):  
Lipid Rafts ◽  
Pluripotent Stem Cells ◽  
Late Onset ◽  
Culture Media ◽  
Cholesterol Levels ◽  
Human Astrocytes ◽  
Human Neurons ◽  
Induced Pluripotent ◽  
Aβ Generation ◽  
Aβ Production

Abstract The onset of Alzheimer’s disease (AD) typically occurs later in life. Importantly, however, recent genetic analysis of patients and unaffected individuals revealed multiple genetic variants associated with late-onset AD. One of the strongest genetic risk factors for AD is 𝜀4 allele of APOE encoding apolipoprotein (ApoE), which is predominantly expressed in glial cells. One of the overarching questions is whether and how this astrocyte-enriched risk factor initiates AD-associated pathology in neurons such as Aβ accumulation and neurodegeneration. Here, we use human induced pluripotent stem cells (hiPSCs) from healthy individuals and isogenic cells in which the ApoE 𝜀3 allele was replaced with an 𝜀4 allele to generate human neurons and astrocytes. We then investigate the effect of astrocytic ApoE4 on the neuronal Aβ production. We find that secretory factors in conditioned media from hiPSC-derived astrocytes carrying APOE4 significantly increased the levels of APP and Aβ secretion in hiPSC-derived neurons. Increasing cholesterol levels in culture media mimicked the effects of ApoE4 ACM by inducing the formation of lipid rafts that potentially provide a physical platform for APP localization on the membrane. We further found that reducing cholesterol levels in ApoE4 ACM with MβCD abolished its effects on neuronal lipid raft expansion and Aβ generation. Our study suggests that ApoE4 astrocytes contribute to amyloidosis by the expansion of lipid rafts and facilitate neuronal Ab production through oversupply of cholesterol.

scholarly journals A proteomic time course through the differentiation of human induced pluripotent stem cells into hepatocyte-like cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tracey Hurrell ◽  
Charis-Patricia Segeritz ◽  
Ludovic Vallier ◽  
Kathryn S. Lilley ◽  
Allan D. Cromarty
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Time Course ◽  
Induced Pluripotent
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