GSE111106 Rostrocaudal Areal Patterning of Human PSC-Derived Cortical Neurons by FGF8 Signaling

In this study, we recapitulated cortical R-C patterning in human pluripotent stem cell (PSC) cultures. Modulation of FGF8 signaling appropriately regulated the R-C markers, and the patterns of global gene expression resembled those of the corresponding areas of in vivo human fetal brains. Furthermore, we demonstrated the utility of this culture system in modeling the area-specific forebrain phenotypes (presumptive upper motor neuron (UMN) phenotypes) of amyotrophic lateral sclerosis (ALS). We anticipate that our culture system will contribute to studies of human neurodevelopment and neurological disease modeling.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

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Publication date: 5 June 2018Source: Stem Cell Reports, Volume 10, Issue 6Author(s): Evangelos Kiskinis, Joel M. Kralj, Peng Zou, Eli N. Weinstein, Hongkang Zhang, Konstantinos Tsioras, Ole Wiskow, J. Alberto Ortega, Kevin Eggan, Adam E. CohenSummaryHuman induced pluripotent stem cell (iPSC)-derived neurons are an attractive substrate for modeling disease, yet the heterogeneity of these cultures presents a challenge for functional characterization by manual patch-clamp electrophysiology. Here, we describe an optimized all-optical electrophysiology, “Optopatch,” pipeline for high-throughput functional characteri...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
AbstractSporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology. Transcriptome ...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
Amyotrophic lateral sclerosis (ALS) is a motor neuron (MN) disease characterized by the loss of MNs in the central nervous system. As MNs die, patients progressively lose their ability to control voluntary mov...
Source: Stem Cell Research and Therapy - Category: Stem Cells Authors: Tags: Research Source Type: research
In conclusion, we here demonstrated for the first time that human TARDBP mutated MNs can be successfully obtained exploiting the reprogramming and differentiation ability of peripheral blood cells, an easily accessible source from any patient.
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: Available online 17 May 2018 Source:Stem Cell Reports Author(s): Evangelos Kiskinis, Joel M. Kralj, Peng Zou, Eli N. Weinstein, Hongkang Zhang, Konstantinos Tsioras, Ole Wiskow, J. Alberto Ortega, Kevin Eggan, Adam E. Cohen Human induced pluripotent stem cell (iPSC)-derived neurons are an attractive substrate for modeling disease, yet the heterogeneity of these cultures presents a challenge for functional characterization by manual patch-clamp electrophysiology. Here, we describe an optimized all-optical electrophysiology, “Optopatch,” pipeline for high-throughput functional characterization ...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
Publication date: Available online 27 April 2018 Source:Stem Cell Research Author(s): Riccardo De Santis, Maria Giovanna Garone, Francesca Pagani, Valeria de Turris, Silvia Di Angelantonio, Alessandro Rosa Human pluripotent stem cells (PSCs) are widely used for in vitro disease modeling. One of the challenges in the field is represented by the ability of converting human PSCs into specific disease-relevant cell types. The nervous system is composed of a wide variety of neuronal types with selective vulnerability in neurodegenerative diseases. This is particularly relevant for motor neuron diseases, in which different moto...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
AbstractMutations in fused in sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS). FUS is a multifunctional protein involved in the biogenesis and activity of several types of RNAs, and its role in the pathogenesis of ALS may involve both direct effects of disease-associated mutations through gain- and loss-of-function mechanisms and indirect effects due to the cross talk between different classes of FUS-dependent RNAs. To explore how FUS mutations impinge on motor neuron-specific RNA-based circuitries, we performed transcriptome profiling of small and long RNAs of motor neurons (MNs) derived from mouse embryonic stem ...
Source: Molecular Neurobiology - Category: Neurology Source Type: research
Abstract Amyotrophic lateral sclerosis (ALS) is incurable and devastating. A dearth of therapies has galvanized experimental focus onto the cellular and molecular mechanisms that both initiate and subsequently drive motor neuron degeneration. A traditional view of ALS pathogenesis posits that disease‐specific injury to a subtype of neurons is mechanistically cell‐autonomous. This “neuron‐centric” view has biased past research efforts. However, a wealth of accumulating evidence now strongly implicates non‐neuronal cells as being major determinants of ALS. Although animal models have proven invaluable in ...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research
This article is protected by copyright. All rights reserved. “Intricate and self‐perpetuating cellular interplay underlies amyotrophic lateral sclerosis (ALS). Disease stage is a key determinant of cell type‐specific molecular mechanisms”.
Source: Stem Cells - Category: Stem Cells Authors: Tags: Embryonic Stem Cells/Induced Pluripotent Stem Cells Source Type: research
Publication date: December 2017 Source:Stem Cell Research, Volume 25 Author(s): Francesca Sironi, Antonio Vallarola, Martina Bruna Violatto, Laura Talamini, Mattia Freschi, Roberta De Gioia, Chiara Capelli, Azzurra Agostini, Davide Moscatelli, Massimo Tortarolo, Paolo Bigini, Martino Introna, Caterina Bendotti Stem cell therapy is considered a promising approach in the treatment of amyotrophic lateral sclerosis (ALS) and mesenchymal stem cells (MSCs) seem to be the most effective in ALS animal models. The umbilical cord (UC) is a source of highly proliferating fetal MSCs, more easily collectable than other MSCs. Recently ...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
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