Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell transcriptomics reveals conserved regulatory networks in human and mouse interneuron development

ABSTRACT: Inhibitory GABAergic interneurons originate in the embryonic medial ganglionic eminence (MGE) and control network activity in the neocortex. Dysfunction of these cells is believed to lead to runaway excitation underlying seizure-based neurological disorders such as epilepsy, autism and schizophrenia. Despite their importance in heath and disease, our knowledge about the development of this diverse neuronal population remains incomplete. Here we conducted single cell RNA sequencing (scRNA-seq) of human fetal MGE from 10 to 15 weeks post conception. These MGE tissues are composed of largely cycling progenitors and immature post-mitotic interneurons with characteristic regional marker expression. Analysis of integrated human and mouse MGE data revealed species conserved transcriptomic profiles and regulatory program. Moreover, we identified novel candidate transcription regulators for human interneuron differentiation. These findings provide a framework for in vitro modelling of interneuron development and strategy for potentially enhance interneurons production from human pluripotent stem cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE230467 | GEO | 2023/04/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Assessment of chromatin state changes during human cortical interneuron development

Project description:We have used our protocol for generating cortical interneurons from human embryonic stem cells to study chromatin state changes during cortical interneuron development. This allows for the identification of cis-regulatory elements and transcription factors which play important roles in this process. Samples were collected at day 0 (hESCs), day 15 (ventral telencephalic patterned medial ganglionic eminence-like (MGE) progenitors), day 35 (immature interneurons), and day 60 (mature interneurons). Day 15 dorsal telencephalic cortical-like neural progenitors were also obtained by using a dual Smad inhibition protocol for comparison with ventral telencephalic MGE-like progenitors.

2024-04-18 | GSE239400 | GEO

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.

2017-05-19 | GSE99049 | GEO

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

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.

2017-07-21 | GSE98201 | GEO

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

2017-07-21 | GSE97880 | GEO

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

2017-07-21 | GSE97881 | GEO

MicroArray Gene Expression Profiling of NKX2.1-GFP+ MGE-like Interneuron Precursors Derived from Human Embryonic Stem Cells

Project description:Human embryonic stem cells with a GFP reporter knock-in into the NKX2.1 locus were differentiated and purified by FACS sorting for global gene expression analysis. Directed differentiation from human pluripotent stem cells (hPSCs) has seen significant progress in recent years. Most differentiated populations, however, exhibit immature properties of an early embryonic stage, raising concerns about their ability to model and treat disease. Here, we report the directed differentiation of hPSCs into medial ganglionic eminence (MGE)-like progenitors and their maturation into forebrain type interneurons. We find that early stage progenitors progress via a radial glial-like stem cell enriched in the human fetal brain. Both in vitro and post-transplantation into the rodent cortex, the MGE-like cells develop into GABAergic interneuron subtypes with mature physiological properties along a prolonged intrinsic timeline of up to seven months, mimicking endogenous human neural development. MGE-derived cortical interneuron deficiencies are implicated in a broad range of neurodevelopmental and degenerative disorders, highlighting the importance of these results for modeling human neural development and disease. Human embryonic stem cells with a GFP reporter knock-in into the NKX2.1 locus were differentiated for 20, 35, and 55 days in vitro and GFP+ cells were purified by FACS sorting. Total RNA was prepared from each timepoint and compared to undifferentiated human embryonic stem cells. hESC = one sample and three technical replicates. D20 = three independent samples. D35 = one sample and two technical replicates. D55 = one sample and one technical replicate.

2013-05-03 | E-GEOD-45660 | biostudies-arrayexpress

Assessment of gene expression changes during human cortical interneuron development

Project description:We have used our protocol for generating cortical interneurons from human embryonic stem cells (hESCs) to study gene expression changes during this process, to identify regulatory networks critical to cortical interneuron development. Samples were collected at day 0 (hESCs), day 15 (ventral telencephalic patterned medial ganglionic eminence-like progenitors), day 35 (immature interneurons), and day 60 (mature interneurons).

2024-04-18 | GSE239396 | GEO

Interneuron origin and molecular diversity in the human fetal brain

Project description:GABAergic inhibitory neurons are crucial in maintaining the stability of neural circuits through synaptic inhibition in the human brain. In this study, we used single-cell RNA sequencing to profile the transcriptomes of fetal cells collected along an early developmental time course to clarify the origin and diversification of interneurons. The heterogeneity of interneurons within the human subpallium is observed in ganglionic eminence precursors and driven by a string of gene regulatory networks that exhibit evident differences in the subventricular zone during the late first trimester. We identified conserved molecular signatures between the cardinal interneuron subtypes of ganglionic eminence precursors and adult interneurons through comparing embryonic and mature cortex data sets.

2021-08-10 | GSE165388 | GEO

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.

2014-09-29 | E-GEOD-60402 | biostudies-arrayexpress

MicroArray Gene Expression Profiling of NKX2.1-GFP+ MGE-like Interneuron Precursors Derived from Human Embryonic Stem Cells

2013-05-03 | GSE45660 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data