Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors

Ehrlich, Marc; Mozafari, Sabah; Glatza, Michael; Starost, Laura; Velychko, Sergiy; Hallmann, Anna Lena; Cui, Qiao Ling; Schambach, Axel; Kim, Kee-Pyo; Bachelin, Corinne; Marteyn, Antoine; Hargus, Gunnar; Johnson, Radia Marie; Antel, Jack P.; Sterneckert, Jared; Zaehres, Holm; Schöler, Hans R.; Evercooren, Anne Baron-Van; Kuhlmann, Tanja

doi:10.1073/pnas.1614412114

Cited by 208 publications

(267 citation statements)

References 51 publications

(85 reference statements)

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“…Initial publications demonstrated that overexpression of OLIG2 or SOX10 can promote the differentiation of human fetal NPC into OPC in vitro as well as their differentiation into MBP+ myelin‐forming cells after transplantation (Maire et al, ; Wang et al, ). We showed that combining the overexpression of SOX10, OLIG2 and NKX6.2 in iPSC derived NPC facilitated OPC specification and led to generation of 70% O4+ cells within 28 days (Ehrlich et al, ) (Figure ). One year later, Garcia‐Leon et al reduced the cocktail of transcription factors by showing that SOX10 alone was sufficient to generate 50 to 60% O4+ cells in 22 days upon iPSC differentiation (Garcia‐Leon et al, ).…”

Section: Generation Of Oligodendrocytes From Pluripotent Cellsmentioning

confidence: 96%

Stem cell derived oligodendrocytes to study myelin diseases

Chanoumidou

Mozafari

Evercooren

et al. 2019

Glia

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Oligodendroglial pathology is central to de‐ and dysmyelinating, but also contributes to neurodegenerative and psychiatric diseases as well as brain injury. The understanding of oligodendroglial biology in health and disease has been significantly increased during recent years by experimental in vitro and in vivo preclinical studies as well as histological analyses of human tissue samples. However, for many of these diseases the underlying pathology is still not fully understood and treatment options are frequently lacking. This is at least partly caused by the limited access to human oligodendrocytes from patients to perform functional studies and drug screens. The induced pluripotent stem cell technology (iPSC) represents a possibility to circumvent this obstacle and paves new ways to study human disease and to develop new treatment options for so far incurable central nervous system (CNS) diseases. In this review, we summarize the differences between human and rodent oligodendrocytes, provide an overview of the different techniques to generate oligodendrocytes from human progenitor or stem cells and describe the results from studies using iPSC derived oligodendroglial lineage cells. Furthermore, we discuss future perspectives and challenges of the iPSC technology with respect to disease modeling, drug screen, and cell transplantation approaches.

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Section: Generation Of Oligodendrocytes From Pluripotent Cellsmentioning

confidence: 96%

Stem cell derived oligodendrocytes to study myelin diseases

Chanoumidou

Mozafari

Evercooren

et al. 2019

Glia

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“…S6B). To extend the analysis to human cells, we generated oligodendrocytes from induced pluripotent human stem cells (iPSCs) derived from healthy human adults (29). We found that BCAS1 was expressed in 86.1 ± 2.3% of the O4 + oligodendrocytes with arborized morphology at 24 days in vitro ( fig.…”

Section: Bcas1 + Cells Represent a Transient Population Of Oligodendrmentioning

confidence: 99%

BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions

et al. 2017

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“…While most oligodendrocyte differentiation protocols take a long period of time (60-150 days; e.g.) and show limited efficiency (Wang et al, 2013;Douvaras et al, 2014;Djelloul et al, 2015), a recent protocol published in PNAS allows rapid and efficient generation of oligodendrocytes from hiPSC (Ehrlich et al, 2017). …”

Section: Published In Vitro Methods Beyond Chemical Testingmentioning

confidence: 99%

Literature review and appraisal on alternative neurotoxicity testing methods

Masjosthusmann

Barenys

El‐Gamal

et al. 2018

EFSA Supporting Publications

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The goal of this review was the evaluation of information on assessment methods in the field of alternative neurotoxicity (NT) testing. We therefore performed a systematic and comprehensive collection of scientific literature (in English) from the past 27 years until mid of 2017 on state of the art alternative testing methods including in vitro test methods, in silico methods and alternative non-mammalian models. This review identified a variety of test methods that have the ability to predict NT of chemicals based on predefined key NT endpoint categories (27). Those endpoint categories were derived from the Mode of Action (MoA) of known human neurotoxicants. Pre-evaluated MoAs of human neurotoxicants allowed the identification of performance characteristics with regard to the ability of a test system to correctly predict a chemical effect on an endpoint category. The most predictive in vitro model that covers a large variety of endpoint categories are primary rodent cells or tissues. Human based systems derived from induced pluripotent stem cells (iPSC) are promising and warrant human relevance. There is however not yet sufficient data on these models to demonstrate their suitability to reliably substitute primary rodent cells for NT testing purposes. Test methods for glia toxicity are rare and glia endpoint categories are clearly underrepresented. Therefore, a focus for future method development should be placed on glia, astrocytes, oligodendrocytes and microglia based models, preferably in a co-culture se up. The review on in silico methods, resulted into 54 QSARs publications, relevant for NT, of which 39 on blood brain barrier (BBB) permeation. The QSARs available in the publications were developed from data on drugs and chemicals, but there appears a limited set of experimental data for chemicals and pesticides on blood-brain barrier passage. The evaluation of NT methods using alternative whole organism approaches demonstrated a majority of data for C. elegans (nematode species), represented with high true prediction (96%). The main endpoint category was inhibition of cholinergic transmission, with specific endpoints for AChE activity and motor activity, the latter confirming the added value of a whole organism approach among alternative models. Though D. rerio, the zebrafish model appeared a www.efsa.europa.eu/publications 2 EFSA Supporting publication 2018:EN-1410The present document has been produced and adopted by the bodies identified above as authors. This task has been carried out exclusively by the authors in the context of a contract between the European Food Safety Authority and the authors, awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights ...

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Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors

Cited by 208 publications

References 51 publications

Stem cell derived oligodendrocytes to study myelin diseases

Stem cell derived oligodendrocytes to study myelin diseases

BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions

Literature review and appraisal on alternative neurotoxicity testing methods

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