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Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Striatal medium spiny neurons (MSN) are critically involved in motor control, and their degeneration is a principal component of Huntingtons disease. We find that the transcription factor Ctip2 (also known as Bcl11b) is central to MSN differentiation and striatal development. Within the striatum, it is expressed by all MSN, while it is excluded from essentially all striatal interneurons. In the absence of Ctip2, MSN do not fully differentiate, as demonstrated by dramatically reduced expression of a large number of MSN markers, including DARPP-32, FOXP1, Chrm4, Reelin, MOR1, GluR1, and Plexin-D1. Furthermore, MSN fail to aggregate into patches, resulting in severely disrupted patch-matrix organization within the striatum. Finally, heterotopic cellular aggregates invade the Ctip2-/- striatum suggesting a failure by MSN to repel these cells in the absence of Ctip2. In order to investigate the molecular mechanisms that underlie Ctip2-dependent differentiation of MSN and that underlie the patch-matrix disorganization in the mutant striatum, we directly compared gene expression between wild type and mutant striatum at P0. Because CTIP2-expressing MSN constitute 90-95% of the neurons within the striatum, we reasoned that we should be able to detect changes in medium spiny neuron gene expression in Ctip2 null mutants. We microdissected out small regions of striatum at matched locations in wild type and Ctip2-/- mutant littermates at P0 and investigated gene expression with Affymetrix microarrays. We selected the 153 most significant genes and further analyzed them to identify a smaller set of genes of potentially high biological relevance. In order to verify the microarray data and define the distribution of the identified genes in the striatum, we performed in situ hybridization or immunohistochemistry for 12 selected genes: Plexin-D1, Ngef, Nectin-3, Kcnip2, Pcp4L1, Neto1, Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, and Neurotensin. We find that all these genes are either specifically downregulated (Plexin-D1, Ngef, Nectin-3 Kcnip2, Pcp4L1, Neto1), or upregulated (Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, Neurotensin), in the Ctip2-/- striatum, confirming and extending the microarray results. Together, these data indicate that Ctip2 is a critical regulator of MSN differentiation, striatal patch development, and the establishment of the cellular architecture of the striatum.
Publication Title
Ctip2 controls the differentiation of medium spiny neurons and the establishment of the cellular architecture of the striatum.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 38 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
3 subtypes of cortical projection neurons were purified by fluorescence-activated cell sorting at 4 different stages of development from mouse cortex. A detailed description of the data set is described in Arlotta, P et al (2005).
Publication Title
Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
3 subtypes of cortical projection neurons were purified by fluorescence-activated cell sorting (FACS) at 4 different stages of development from mouse cortex. A detailed description of the data set is described in Arlotta, P et al (2005) and Molyneaux, BJ et al (2009). The hybridization cocktails used here were originally applied to the Affymetrix mouse 430A arrays and submitted as GEO accession number GSE2039. The same hybridization cocktails were then applied to the Affymetrix mouse 430 2.0 arrays, and those data are contained in this series.
Publication Title
Novel subtype-specific genes identify distinct subpopulations of callosal projection neurons.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Corticospinal motor neurons (CSMN) are one specialized class of cortical excitatory neurons, which connect layer Vb of the cortex to the spinal cord. a master transcription factor Forebrain expressed zinc finger 2 (Fezf2) has been identified that is necessary for the fate specification of CSMN. Fezf2 alone can cell-autonomously instruct the acquisition of CSMN-specific features when expressed in diverse, permissive cellular contexts, in vivo.
Publication Title
Gene co-regulation by Fezf2 selects neurotransmitter identity and connectivity of corticospinal neurons.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 212 Downloadable Samples
IlluminaHiSeq2500
Description
Long noncoding RNAs (lncRNAs) have been implicated in numerous cellular processes including brain development. Yet the in vivo expression dynamics and molecular pathways regulated by these molecules are less well understood. Here, we leveraged a cohort of 13 lncRNA null-mutant mouse models to investigate the spatio-temporal expression of lncRNAs in the developing and adult brain. We observed a wide range of different spatio-temporal expression profiles in the brain. Several lncRNAs are differentially expressed both in time and space, and others present highly restricted expression in only selected brain regions. We further explore the consequent transcriptome alterations after loss of these lncRNA loci, and demonstrate altered regulation of a large variety of cellular pathways and processes. We further found that 6/13 lncRNA null-mutant strains significantly affect the expression of several neighboring protein-coding genes, in a cis-like manner. This resource provides insight into the expression patterns and potential effect of lncRNA loci in the developing and adult mammalian brain, and allows future examination of the specific functional relevance of these genes in neural development, brain function, and disease. We have sequenced wildtype and mutant whole brains from a cohort of 13 lncRNA knockout mouse strains at two developmetal timepoints (E14.5 and adult). Overall design: Comparison between wildtype and mutant whole brains transcriptomes in 13 lncRNA mutant strains at two different timepoints. Please note that for each knockout strain there are KO_E14.5 and KO_Adult samples, however for WT, each KO strain was compared to a cohort of 14 WTs (N3 background) and 3 WTs (N2.5 background) at either Adult or E14.5 timepoint. So in total there are 14 WT_Adult and 14 WT_E14.5 and in each differential analysis the 2 or 3 KOs (in N3 background) were compared to this entire cohort at the respective timepoint; a cohort of 3 WT_adult (N2.5) or 3 WT_E14.5 samples compared to other N2.5 KO samples at the respective timepoint. Thus, each processed data file was generated by comparing each KO strain to a cohort of WTs (at either Adult or E14.5 timepoint; ko_vs_WT_Adult or ko_vs_WT_embryonic). The mouse strain (background) used in these experiments a cross between 129 and C57BL/6 in the third generation (N3) of breeding in the C57BL/6 line, with the exception of the KANTR mice, which are N2.5.
Publication Title
Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE55079- Rattus norvegicus
- 36 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Loss of functional -cell mass is a hallmark of Type 1 and Type 2 diabetes, and methods for restoring these cells are needed. Nkx6.1 induces -cell proliferation, but the pathway by which Nkx6.1 activates -cell expansion has not been defined. Here we demonstrate that Nkx6.1 induces expression of the Nr4a1 and Nr4a3 orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated -cell proliferation. Overexpression of the Nr4a receptors results in increased expression of key cell cycle inducers E2F1 and cyclin E1. Furthermore, Nr4a receptors induce components of the anaphase-promoting complex, including Ube2c.
Publication Title
Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Loss of functional -cell mass is a hallmark of Type 1 and Type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor Nkx6.1 in rat pancreatic islets induces -cell proliferation and enhances glucose-stimulated insulin secretion, but the pathway by which Nkx6.1 activates -cell expansion has not been defined. Here we demonstrate that Nkx6.1 induces expression of the Nr4a1 and Nr4a3 orphan nuclear receptors, and that these factors are both necessary and sufficient for Nkx6.1-mediated -cell proliferation. Consistent with this finding, global knockout of Nr4a1 results in a decrease in -cell area in neonatal and young mice. Overexpression of Nkx6.1 and the Nr4a receptors results in increased expression of key cell cycle inducers E2F1 and cyclin E1. Furthermore, Nkx6.1 and Nr4a receptors induce components of the anaphase-promoting complex, including Ube2c, resulting in degradation of the cell cycle inhibitor p21CIP1. These studies identify a new bipartite pathway for activation of -cell proliferation, suggesting several new targets for expansion of functional -cell mass.
Publication Title
Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 412 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2500
Description
We report that combining NGN2 programming with SMAD and WNT inhibition generates patterned induced neurons (hpiNs).Transcriptional analyses showed that hpiN cultures contained cells along a developmental continuumranging from poorly differentiated neuronal progenitors to well-differentiated, excitatory glutamatergic neurons. The most differentiated neurons could be identified using a CAMK2A::GFP reporter gene. Overall design: RNA sequencing analysis (population and single cell) over hpiNs differentiation time (D0 through D49 after induction). Two independent iPS lines, 9 time points, three replicates each.
Publication Title
Combining NGN2 Programming with Developmental Patterning Generates Human Excitatory Neurons with NMDAR-Mediated Synaptic Transmission.
Sample Metadata Fields
Specimen part, Disease, Cell line, Subject, Time
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