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GSE58614
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Developmental regulation of gliogenesis in the mammalian CNS is incompletely understood, in part due to a limited repertoire of lineage-specific genes. We used Aldh1l1-GFP as a marker for gliogenic radial glia and later-stage precursors of developing astrocytes and performed gene expression profiling of these cells. We then used this dataset to identify candidate transcription factors that may serve as glial markers or regulators of glial fate. Our analysis generated a database of developmental stage-related markers of Aldh1l1+ cells between murine embryonic day 13.5-18.5. Using these data we identify the bZIP transcription factor Nfe2l1 and demonstrate that it promotes glial fate under direct Sox9 regulatory control. Thus, this dataset represents a resource for identifying novel regulators of glial development.
Publication Title
Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The progression from stem cell to differentiated neuron is associated with extensive chromatin remodeling that controls gene expression, but the mechanisms that connect chromatin to gene expression are not well defined. Here we show that mutation of ZNF335 causes severe human microcephaly ("small brain"), small somatic size, and neonatal death. Germline Znf335 null mutations are embryonically lethal in mice, whereas RNA-interference studies and postmortem human studies show that Znf335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. Znf335 is a component of a vertebrate-specific, trithorax H3K4 methylation complex, while global ChIP-seq and mRNA expression studies show that Znf335 is a previously unsuspected, direct regulator of REST/NRSF, a master regulator of neural gene expression and neural cell fate, as well as other essential neural-specific genes. Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF, and provide the first direct evidence that this pathway regulates human neurogenesis and neuronal differentiation.
Publication Title
Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two murine Neurogenin transcription factors in human induced pluripotent stem cells, and obtained neurons with bipolar morphology in four days at greater than 90% purity. The high purity enabled mRNA and microRNA expression profiling during neurogenesis, thus revealing the genetic programs involved in the transition from stem cell to neuron. These profiles were then analyzed to identify the regulatory networks underlying the differentiation of the neurons. Overall design: Paired end RNA sequencing of iPS cells (PGP1) at 0, 1, 3, and 4 days post- doxycycline induction of murine NGN1 and NGN2. This was done using an Illumina HiSeq, and reads were aligned to hg19
Publication Title
Rapid neurogenesis through transcriptional activation in human stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 176 Downloadable Samples
- Illumina HiSeq 2500
Description
We report the application of low cell number sequencing of identifiable Drosophila melanogaster neurons following behavior. We demonstate the feasibility of identifying the transcriptome of 5 Mushroom Body output Neurons and 2 classes of Kenyon Cells. We find these neurons display a diverse repertoire of receptors and signaling transcripts. This information alone seems to be enough to identify each class of neurons in the study. In additional we show that aversive long-term memory induces changes in gene transcript levels in a subset of these neurons. This study provides a framework for identifying neuronal classes in Drosophila melanogaster and gaining insight into the interplay between behavior and gene regulation. Overall design: 5 Mushroom Body output neurons and 2 classes of kenyon cells are used to look at general gene expression and changes following aversive long term memory. Paired control and trained animals were used and a minimum of 4 pairs up to 6 pairs. Animals were of the same background (w1118). Animals were aged and parental matched. Cells were harvested at the same chronological time for the animals across all experiments. All animals were exposed to 1 minute of each odor and 1 minute of a series of 12 5second 60V shocks. This was considered one block and then the animals had spaced training of each block so there was a 10 minute break between 8 blocks of training. Trained animals had an odor paired with a shock, control animals received the shock then the odor stimulus. All cells were harvested usign a patch pipet from living animals on an electrophysiology rig within a half hour of the end of training. Cells were amplified using the Clontech SMARTer Ultra Low Input RNA version 2 High Volume kit. 2 Brain samples were also collected and 3-4 whole fly samples for each genotype were collected to account for background differences across flies.
Publication Title
Cell-Type-Specific Transcriptome Analysis in the Drosophila Mushroom Body Reveals Memory-Related Changes in Gene Expression.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Bcl11a is a transcription factor known to regulate lymphoid and erythroid development. Recent bioinformatic analysis of global gene expression patterns has suggested a role for Bcl11a in the development of dendritic cell (DC) lineages. We tested this hypothesis by analyzing the development of DC and other lineages in Bcl11a(-/-) mice. We show that Bcl11a is required for expression of IL-7 receptor (IL-7R) and Flt3 in early hematopoietic progenitor cells. The loss of IL-7R(+) common lymphoid progenitors accounts for previously described lymphoid defects in Bcl11a(-/-) mice. In addition, we found severely decreased numbers of plasmacytoid dendritic cells (pDCs) in Bcl11a(-/-) fetal livers and in the bone marrow of Bcl11a(-/-) fetal liver chimeras. Moreover, Bcl11a(-/-) cells show severely impaired in vitro development of Flt3L-derived pDCs and classical DCs (cDCs). In contrast, we found normal in vitro development of DCs from Bcl11a(-/-) fetal liver cells treated with GM-CSF. These results suggest that the persistent cDC development observed in Bcl11a(-/-) fetal liver chimeras reflects derivation from a Bcl11a- and Flt3-independent pathway in vivo.
Publication Title
Bcl11a controls Flt3 expression in early hematopoietic progenitors and is required for pDC development in vivo.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
The myeloma bone marrow microenvironment promotes proliferation of malignant plasma cells and resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells. Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not enhance ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells stimulate a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients. Overall design: Single-end 50 bp RNA-seq of MM.1S myeloma cell line either grown alone in monoculture, MM.1S isolated after 24 hr co-culture with immortalized HS5 bone marrow stromal cells, or HS5 bone marrow stromal cells grown alone
Publication Title
Repurposing tofacitinib as an anti-myeloma therapeutic to reverse growth-promoting effects of the bone marrow microenvironment.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The present study reveals LMYC and MXD1 as novel regulators of a transcriptional program that is modulated during the maturation of Batf3-dependent dendritic cells (also known as type I classical dendritic cells or cDC1s).
Publication Title
The MYCL and MXD1 transcription factors regulate the fitness of murine dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
ES cells differentiated in the presence of the Wnt inhibitor DKK1 fail to express the transcription factor Snail and undergo EMT or mesoderm differentiation. We generated an ES cell line, A2.snail, that induced Snail expression upon addition of doxycycline addition.
Publication Title
Snail promotes the cell-autonomous generation of Flk1(+) endothelial cells through the repression of the microRNA-200 family.
Sample Metadata Fields
Specimen part, Cell line
View Samples