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Comparison of gene expression signature between nascent Lhx6-GFP+ cells from mouse embryonic brain and differentiated Lhx6-GFP+ cells from ES cells (as well as comparing those of Lhx6-GFP+ and Lhx6-GFP- cells from ES cells)

ABSTRACT: There was a remarkable similarity in the molecular properties of the MGE-GFP+ and ES-GFP+ cells. In particular, genes that are important for medial ganglionic eminence (MGE) and cortical interneurons development are both high in expression in both MGE-Lhx6-GFP+ and ES-Lhx6-GFP+ cells (compared to ES-Lhx6-GFP- cells).

ORGANISM(S): Mus musculus

PROVIDER: GSE43508 | GEO | 2013/01/16

SECONDARY ACCESSION(S): PRJNA186616

REPOSITORIES: GEO

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Comparison of gene expression signature between nascent Lhx6-GFP+ cells from mouse embryonic brain and differentiated Lhx6-GFP+ cells from ES cells (as well as comparing those of Lhx6-GFP+ and Lhx6-GFP- cells from ES cells)

Project description:There was a remarkable similarity in the molecular properties of the MGE-GFP+ and ES-GFP+ cells. In particular, genes that are important for medial ganglionic eminence (MGE) and cortical interneurons development are both high in expression in both MGE-Lhx6-GFP+ and ES-Lhx6-GFP+ cells (compared to ES-Lhx6-GFP- cells). To investigate how closely ES cells-derived Lhx6-GFP+ cells resembled authentic Lhx6+ MGE cells, and to define the molecular properties of the Lhx6-GFP+ and Lhx6-GFP- cells from differentiated ES cells, we compared their gene expression profiles. We used FACS to purify GFP+ cells from the E12.5 MGE of Lhx6-GFP transgenic mice. ES-Lhx6-GFP+ cells and ES-Lhx6-GFP- cells (both from D12 EB aggregates) were also isolated by fluorescent activated cell sorting (FACS) and all of the RNA samples were subjected to RNA expression microarray analyses.

2013-01-16 | E-GEOD-43508 | biostudies-arrayexpress

Next Generation Sequencing analysis of Lhx6 heterozygote and null forebrain transcriptomes at post natal day 15

Project description:Here we characterize the changes in the forebrain transcriptome resulting from the deletion of the transcription factor Lhx6, generated by RNA-seq technology with biologic replication. Lhx6 is an essential regulatory gene in the development of cortical interneurons generated in the medial ganglionic eminences of the embryonic brain. This data contains insights into gene networks important for the development of medial ganglionic eminence derived interneurons.

2017-12-16 | GSE108161 | 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

Development of LHX6-inducible system in PK-1 and PK-9 cells

Project description:Epigenetic gene silencing by aberrant DNA methylation leads to loss of key cellular pathways in tumorigenesis. DNA methylation-mediated silenced genes in pancreatic cancer were searched by methyl-CpG targeted transcriptional activation (MeTA) method and LHX6 (LIM homeobox 6), a transcription factor involved in embryogenesis and head development, was selected as one of candidate genes. LHX6 was downregulated in most pancreatic cancer cell lines (83%: 10/12) mainly through promoter hypermethylation and histone deacetylation. Furthermore, LHX6 was also methylated in primary pancreatic cancers in a tumor-specific manner (57%: 16/28). In order to assess the biological significance of LHX6 in pancreatic tumorigenesis, we first performed colony formation assay and found that LHX6 re-expression inhibited colony formation in pancreatic cancer cell lines. Similarly, inducible expression of LHX6 inhibited cell proliferation and migration in LHX6 low-expressing pancreatic cancer cell lines. On the other hand, knockdown of LHX6 accelerated cell proliferation in LHX6 high-expressing pancreatic cancer cell lines. Our present results suggest that epigenetic inactivation of LHX6 plays an important role in pancreatic tumorigenesis by promoting cell proliferation.

2020-10-11 | GSE135736 | 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

Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons (ChIP-Seq)

Project description:The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors (TFs), regulatory elements (REs), and chromatin are thought to precisely regulate gene expression. In the medial ganglionic eminence (MGE), the NKX2-1 TF controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and forebrain interneurons. We dissected the molecular functions of NKX2-1 by defining its chromosomal binding regions, regulation of gene expression and epigenetic state. NKX2-1 binding at distal REs led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, Nkx2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub- ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach provides a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.

2016-09-21 | GSE85704 | GEO

Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons (microarray)

2016-09-21 | GSE85703 | GEO

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

2013-05-03 | GSE45660 | GEO

Embryonic stem cells-derived neural progenitor cells

Project description:J14 ES cells differentiated into MGE-like cells. Three groups of single-cell preparations were analyzed: ES cells (undifferentiated), differentiated cells (unsorted, of which less than 10% are GFP+) and GFP+ differentiated cells. These are specified in the "group" sample characteristic, with values "ES", "Unsorted" and "GFP+" respectively. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0007904

2017-03-02 | GSE94579 | GEO

MTG8 interacts with LHX6 to specify cortical interneuron subtype identity

Project description:In the study we compared migrating embryonic cortical interneurons from control mouse embryos and ones carryng homozygous deletions of either Mtg8 or Lhx6. The aim was to identify genes that are co-regulated by LHX6 and MTG8.

2022-08-21 | GSE195743 | GEO

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