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Modeling Human Cortical Development in vitro using induced Pluripotent Stem Cells

ABSTRACT: Human iPSCs grown in suspension in the presence of rostral neuralizing factors generated three-dimensional structures containing polarized radial glia, intermediate progenitors and a spectrum of layer-specific cortical neurons reminiscent of their organization in vivo. The hiPSC-derived multilayered structures express a gene expression profile typical of the embryonic telencephalon, but not that of other CNS regions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE41565 | GEO | 2012/10/19

SECONDARY ACCESSION(S): PRJNA177962

REPOSITORIES: GEO

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Modeling Human Cortical Development in vitro using induced Pluripotent Stem Cells

Project description:Human iPSCs grown in suspension in the presence of rostral neuralizing factors generated three-dimensional structures containing polarized radial glia, intermediate progenitors and a spectrum of layer-specific cortical neurons reminiscent of their organization in vivo. The hiPSC-derived multilayered structures express a gene expression profile typical of the embryonic telencephalon, but not that of other CNS regions. Total RNA obtained from iPSC lines and H1 line was submitted for microarray analysis using HumanHT-12 v4 BEADCHIP (Illumina).

2012-10-19 | E-GEOD-41565 | biostudies-arrayexpress

Expression data from rostral forebrains of wild-type and Fezf1-/- Fezf2-/- mice

Project description:Zinc-finger genes Fezf1 and Fezf2 encode transcriptional repressors. Fezf1 and Fezf2 are expressed in the early neural stem/progenitor cells and control neuronal differentiation in mouse dorsal telencephalon. We compared gene expression profiles of rostral forebrains, which contain the telencephalon and the rostral part of the diencephalon, from embryonic day (E) 9.5, E10.5, and E12.5 wild-type control and Fezf1-/- Fezf2 -/- mouse embryos. The forebrain rostral to the caudal limit of the lateral ventricles was isolated manually from E9.5, E10.5, and E12.5 wild-type and Fezf1-/- Fezf2-/- mice. Total RNAs were isolated by Separsol-RNA I and were used for microarray analyses.

2010-04-12 | E-GEOD-21156 | biostudies-arrayexpress

Expression data from rostral forebrains of wild-type and Fezf1-/- Fezf2-/- mice

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Self-organization of polarized cerebellar plate neuroepithelium in three-dimensional culture of human pluripotent stem cells

Project description:During cerebellar development, the main portion of the cerebellar plate neuroepithelium (NE) gives birth to Purkinje cells and interneurons, while the germinal zone at its dorsal edge, called the rhombic lip (RL), generates granule cells and cerebellar nuclei neurons. However, it remains elusive how these components work together to generate the intricate structure of the cerebellar anlage. In this study, we found that a polarized cerebellar anlage structure self-organizes in three-dimensional (3D) human ES cell (hESC) culture. This NE is capable of differentiating into electrophysiologically functional Purkinje cells. The addition of FGF19 promotes spontaneous generation of dorsoventrally polarized NE structures containing cerebellar and basal plates. Furthermore, further addition of SDF1 promoted the generation of stratified cerebellar plate NE with RL-like germinal zones self-forming at the edge. Thus, hESC-derived cerebellar progenitors exhibit substantial self-organizing potential for generating a polarized structure reminiscent of the early human cerebellar anlage at the first trimester. Examination of mRNA profile in two different treated human ES cells .

2015-04-15 | E-GEOD-63015 | biostudies-arrayexpress

Self-organization of polarized cerebellar plate neuroepithelium in three-dimensional culture of human pluripotent stem cells

2015-04-15 | GSE63015 | GEO

Self-patterning of rostral-caudal neuroectoderm requires dual role of Fgf signaling for localized Wnt antagonism

Project description:The neuroectoderm is patterned along a rostral-caudal axis in response to localized factors in the embryo, but exactly how these factors act as positional information for this patterning is not yet fully understood. Here, using the self-organizing properties of mouse embryonic stem cell (ESC), we report that ESC-derived neuroectoderm self-generates a Six3+ rostral and a Irx3+ caudal bipolarized patterning. In this instance, localized Fgf signaling performs dual roles, as it regulates Six3+ rostral polarization at an earlier stage and promotes Wnt signaling at a later stage. The Wnt signaling components are differentially expressed in the polarized tissues, leading to genome-wide Irx3+ caudal-polarization signals. Surprisingly, differentially expressed Wnt agonists and antagonists have essential roles in orchestrating the formation of a balanced rostral-caudal neuroectoderm pattern. Together, our findings provide key processes for dynamic self-patterning and evidence that a temporally and locally regulated interaction between Fgf and Wnt signaling controls self-patterning in ESC-derived neuroectoderm.

2017-08-05 | GSE72520 | GEO

Otx2 controls regional patterning within the MGE and regional identity of the septum [ChIP-Seq]

Project description:The Otx2 homeobox transcription factor is essential for gastrulation and early neural development. We generated Otx2 conditional knockout (cKO) mice to investigate its roles in telencephalon development after E9.0. We conducted transcriptional profiling and in situ hybridization to identify genes de-regulated in Otx2 cKO ventral forebrain. In parallel, we used ChIP-seq to identify enhancer elements, OTX2 binding motif, and which de-regulated genes are likely direct targets of Otx2 transcriptional regulation. We found that Otx2 was essential in septum specification; regulation of Fgf signaling in the rostral telencephalon; and medial ganglionic eminence (MGE) patterning, neurogenesis, and oligodendrogenesis. Within the MGE, Otx2 was required for ventral but not dorsal identity; this is the first demonstration of a transcription factor that contributes to regional patterning within the MGE. Microdissected subpallium (septum, MGE, and LGE ) from wildtype E12.5 CD-1 embryos was used in three independentanti-OTX2 ChIP-seq experiments.

2015-06-10 | E-GEOD-69724 | biostudies-arrayexpress

Otx2 controls regional patterning within the MGE and regional identity of the septum [ChIP-Seq]

2015-06-10 | GSE69724 | GEO

Otx2 controls regional patterning within the MGE and regional identity of the septum [Agilent]

2015-06-03 | GSE69547 | GEO

Project description:"Expression profiling on the mouse E11.5 rostral telencephalon of Emx1Cre;Gli3 conditional mutants"

| PRJEB7343 | ENA