Directed Differentiation of Human Embryonic Stem Cells into Neural Progenitors

Banda, Erin; Grabel, Laura

doi:10.1007/7651_2014_67

Cited by 25 publications

(16 citation statements)

References 17 publications

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“…For example, hESC-derived neural rosettes resemble cell arrangements observed in the neural tube and developing neocortex. This is consistent with the fact that these structures contain gradients of differentiated cell types, with less differentiated neural cells (NPCs) in the center and more mature cells at the basal surface [55].…”

Section: Discussionsupporting

confidence: 60%

A genomics-based framework for identifying biomarkers of human neurodevelopmental toxicity

Robinson

Gormley

Fisher

2017

Reproductive Toxicology

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Human embryonic stem cell (hESC) neural differentiation models have tremendous potential for evaluating environmental compounds in terms of their ability to induce neurodevelopmental toxicity. Genomic based-approaches are being applied to identify changes underlying normal human development (in vitro and in vivo) and the effects of environmental exposures. Here, we investigated whether mechanisms that are shared between hESC neural differentiation model systems and human embryos are candidate biomarkers of developmental toxicities for neurogenesis. We conducted a meta-analysis of transcriptomic datasets with the goal of identifying differentially expressed genes that were common to the hESC-model and human embryos. The overlapping NeuroDevelopmental Biomarker (NDB) gene set contained 304 genes which were enriched for their roles in neurogenesis. These genes were investigated for their utility as candidate biomarkers in the context of toxicogenomic studies focused on the effects of retinoic acid, valproic acid, or carbamazepine in hESC models of neurodifferentiation. The results revealed genes, including 13 common targets of the 3 compounds, that were candidate biomarkers of neurotoxicity in hESC-based studies of environmental toxicants.

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Section: Discussionsupporting

confidence: 60%

A genomics-based framework for identifying biomarkers of human neurodevelopmental toxicity

Robinson

Gormley

Fisher

2017

Reproductive Toxicology

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“…Stable lines of hNPCs were derived from each of the hESC lines used (Supplementary Table S1), following previously described protocols [32][33][34], with slight modifications. In brief, at day 18 of IVND (see IVND of hESCs), the attached cells surrounding excised NRs were dissociated using TrypLE (LifeTech.)…”

Section: Derivation Of Hnpcsmentioning

confidence: 99%

Molecular Mechanisms Regulating Impaired Neurogenesis of Fragile X Syndrome Human Embryonic Stem Cells

Telias

Mayshar

Amit

et al. 2015

Stem Cells and Development

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Fragile X syndrome (FXS) is the most common form of inherited cognitive impairment. It is caused by developmental inactivation of the FMR1 gene and the absence of its encoded protein FMRP, which plays pivotal roles in brain development and function. In FXS embryos with full FMR1 mutation, FMRP is expressed during early embryogenesis and is gradually downregulated at the third trimester of pregnancy. FX-human embryonic stem cells (FX-hESCs), derived from FX human blastocysts, demonstrate the same pattern of developmentally regulated FMR1 inactivation when subjected to in vitro neural differentiation (IVND). In this study, we used this in vitro human platform to explore the molecular mechanisms downstream to FMRP in the context of early human embryonic neurogenesis. Our results show a novel role for the SOX superfamily of transcription factors, specifically for SOX2 and SOX9, which could explain the reduced and delayed neurogenesis observed in FX cells. In addition, we assess in this study the ''GSK3b theory of FXS'' for the first time in a human-based model. We found no evidence for a pathological increase in GSK3b protein levels upon cellular loss of FMRP, in contrast to what was found in the brain of Fmr1 knockout mice. Our study adds novel data on potential downstream targets of FMRP and highlights the importance of the FX-hESC IVND system.

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“…With this system, we show how to apply traction force microscopy to measure cell–ECM forces in real time as the colonies mature, and also assess how cell–cell forces develop with a technique called monolayer stress microscopy [20], allowing us to generate a comprehensive picture of how forces develop in a developmentally relevant epithelial model system. Many differentiation protocols that begin with human pluripotent stem cells use monolayer culture as a starting point for differentiation [28–32], and it has been shown that both extrinsic and intrinsic cell–matrix forces affect differentiation in other contexts [33,34], so the ability to quantify and manipulate forces could enhance our understanding of how mechanics is involved in many aspects of development.…”

Section: Introductionmentioning

confidence: 99%

Monitoring developmental force distributions in reconstituted embryonic epithelia

Przybyla

Lakins

Sunyer

et al. 2016

Methods

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The way cells are organized within a tissue dictates how they sense and respond to extracellular signals, as cues are received and interpreted based on expression and organization of receptors, downstream signaling proteins, and transcription factors. Part of this microenvironmental context is the result of forces acting on the cell, including forces from other cells or from the cellular substrate or basement membrane. However, measuring forces exerted on and by cells is difficult, particularly in an in vivo context, and interpreting how forces affect downstream cellular processes poses an even greater challenge. Here, we present a simple method for monitoring and analyzing forces generated from cell collectives. We demonstrate the ability to generate traction force data from human embryonic stem cells grown in large organized epithelial sheets to determine the magnitude and organization of cell–ECM and cell–cell forces within a self-renewing colony. We show that this method can be used to measure forces in a dynamic hESC system and demonstrate the ability to map intracolony protein localization to force organization.

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Directed Differentiation of Human Embryonic Stem Cells into Neural Progenitors

Cited by 25 publications

References 17 publications

A genomics-based framework for identifying biomarkers of human neurodevelopmental toxicity

A genomics-based framework for identifying biomarkers of human neurodevelopmental toxicity

Molecular Mechanisms Regulating Impaired Neurogenesis of Fragile X Syndrome Human Embryonic Stem Cells

Monitoring developmental force distributions in reconstituted embryonic epithelia

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