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Medial Ganglionic Eminence and Cortical Organoids Model Human Brain Development and Interneuron Migration

ABSTRACT: Medial Ganglionic Eminence and Cortical Organoids Model Human Brain Development and Interneuron Migration

PROVIDER: PRJNA383130 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR5453680_1.fastq.gz	Fastqsanger.gz
	SRR5453680_2.fastq.gz	Fastqsanger.gz
	SRR5453681_1.fastq.gz	Fastqsanger.gz
	SRR5453681_2.fastq.gz	Fastqsanger.gz

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Medial Ganglionic Eminence and Cortical Organoids Model Human Brain Development and Interneuron Migration [ATAC-seq]

Project description:Organoid techniques provide unique platforms to model brain development and neurological disorders. While organoids recapitulating corticogenesis were established, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, remains to be developed. Here, we describe a system to generate MGE or cortex-specific organoids from human pluripotent stem cells. These organoids recapitulate the developments of MGE and cortex domains respectively. Population and single-cell transcriptomic profiling revealed transcriptional dynamics and lineage productions during MGE and cortical organoids development. Chromatin accessibility landscapes were found to be involved in this process. Furthermore, MGE and cortical organoids generated physiologically functional neurons and neuronal networks. Finally, we applied fusion organoids as a model to investigate human interneuron migration. Together, our study provides a new platform for generating domain-specific brain organoids, for modeling human interneuron migration, and offers deeper insight into molecular dynamics during human brain development.

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Medial Ganglionic Eminence and Cortical Organoids Model Human Brain Development and Interneuron Migration [RNA-seq2]

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Medial Ganglionic Eminence and Cortical Organoids Model Human Brain Development and Interneuron Migration [RNA-seq]

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Sp9 regulates medial ganglionic eminence-derived cortical interneuron development

Project description:In the mammalian cortex, about 60% of GABAergic interneurons, mainly including parvalbumin-expressing (PV+) and somatostatin (SST+) interneurons are generated from the medial ganglionic eminence (MGE) in the subpallium and tangentially migrate to the cortex. Here we analyze the role of the Sp9 transcription factor in regulating the development of MGE-derived cortical interneurons. We show that SP9 is widely expressed in the MGE subventricular zone (SVZ) and in MGE-derived migrating interneurons. By analyzing Sp9 null and conditional mutant mice, we demonstrate that Sp9 promotes MGE progenitor proliferation in the SVZ and is required for the normal patterning of tangential migration and the laminar distribution of MGE-derived cortical GABAergic interneurons. Loss of Sp9 function results in a ~50% reduction of MGE-derived cortical interneurons, an ectopic aggregation of MGE-derived neurons in the embryonic ventral telencephalon, and an increased ratio of SST+/PV+ cortical interneurons. Finally, we provide evidence that Sp9 regulates MGE derived cortical interneuron development through promoting expression of the Lhx6 and Lhx8 transcription factors.

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Comparative expression of embryonic medial- and lateral/caudal-ganglionic eminence cells migrating in the mouse cerebral cortex

Project description:Cortical interneurons originate in the medial and caudal ganglionic eminence and migrate into the cortex during embryogenesis. We purified cells migrating within the cortex at different embryonic stages and compared their transcriptome to identify transcriptional programmes underlying distinct cortical interneuron fates.

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ChIP-seq for TCF4 in human medial ganglionic eminence-like organoids (hMGEOs) derived from ihtc-03 cell line.

Project description:To depict the gene regulatory network of TCF4 in interneuron development, We performed chromatin immunoprecipitation-sequencing (ChIP seq) on human medial ganglionic eminence-like organoids (hMGEOs) to identify genome-wide TCF4 binding sites. This study provides compelling evidence to support the biological rationale linking TCF4 to the developing cortical interneuron.

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Project description:Deep transcriptional profiling of the human neocortex, lateral ganglionic eminence (LGE) and medial ganglionic eminences (MGE), from 7 to 20 post-conceptional weeks (pcw), for de novo lincRNAs discovery and to establish a unique coding and non-coding gene signature for the three different regions.

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CTCF occupancy in the mouse telencephalon and medial ganglionic eminence

Project description:In this study, we wanted to compare CTCF binding sites in whole telencephalon vs medial ganglionic eminence (MGE) at embryonic day E13.5.

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Expression data from purified medial ganglionic eminence (MGE) interneurons, 3 biological replicates

Project description:During development, newborn interneurons migrate throughout the embryonic brain. Here, we provide evidence that these interneurons act in a paracrine fashion to regulate developmental oligodendrocyte formation. Specifically, we show that medial ganglionic eminence (MGE) interneurons secrete factors that promote genesis of oligodendrocytes from glially-biased cortical precursors in culture. Moreover, when MGE interneurons are genetically ablated in vivo prior to their migration, this causes a deficit in cortical oligodendrogenesis. Modeling of the interneuron-precursor paracrine interaction using transcriptome data identifies the cytokine fractalkine as responsible for the pro-oligodendrocyte effect in culture. This paracrine interaction is important in vivo, since knockdown of the fractalkine receptor CX3CR1 in embryonic cortical precursors, or constitutive knockout of CX3CR1 causes decreased numbers of oligodendrocyte progenitor cells (OPCs) and oligodendrocytes in the postnatal cortex. Thus, in addition to their role in regulating neuronal excitability, interneurons act in a paracrine fashion to promote the developmental genesis of oligodendrocytes. We used microarrays to generate a list of expressed genes in purified medial ganglionic eminence (MGE) interneurons

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RNA-seq of laser-capture microdissected 50x50x50 um tissue cubes from the medial ganglionic eminence of wild-type and GFRa1 mutant mice

Project description:Cortical interneurons originating from the medial ganglionic eminence (MGE) are among the most diverse cells within the CNS. Different pools of proliferating progenitor cells are thought to exist in the ventricular zone of the MGE, but whether the underlying subventricular and mantle regions of the MGE are spatially patterned has not yet been addressed. Here, we combined laser-capture microdissection and multiplex RNA-sequencing to map the transcriptome of MGE cells at a spatial resolution of 50 M-BM-5m. Distinct groups of progenitor cells showing different stages of interneuron maturation were identified and topographically mapped based on their genome-wide transcriptional pattern. One 50 M-BM-5m coronal section from the MGE was taken from each of two wildtype and one GFRa1 mutant E12.5 C57bl6/J mouse. Each section was laser microdissected into approximately 100 cubes, covering the whole MGE, and each cube was further processed for RNA-seq analysis.

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