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GSE19372
Mus musculus
18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The aim of this study is to profile gene expression dynamics during the in vitro differentiation of embryonic stem cells into ventral motor neurons. Expression levels were profiled using Affymetrix microarrays at six timepoints during in vitro differentiation: ES cells (Day 0), embryoid bodies (Day 2), retinoid induction of neurogenesis (Day 2 +8hours of exposure to retinoic acid), neural precursors (Day 3), progenitor motor neurons (Day 4), postmitotic motor neurons (Day 7).
Publication Title
Ligand-dependent dynamics of retinoic acid receptor binding during early neurogenesis.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptional programming of cell identity promises to open up new frontiers in regenerative medicine by enabling the efficient production of clinically relevant cell types. We examine if such cellular programming is accomplished by transcription factors that each have an independent and additive effect on cellular identity, or if programming factors synergize to produce an effect that is not independently obtainable. The combinations of Ngn2-Isl1-Lhx3 and Ngn2-Isl1-Phox2a transcription factors program embryonic stem cells to express a spinal or cranial motor neuron identity respectively. The two alternate expression programs are determined by recruitment of Isl1/Lhx3 and Isl1/Phox2a pairs to distinct genomic locations characterized by two alternative dimeric homeobox motifs. These results suggest that the function of programming modules relies on synergistic interactions among transcription factors and thus cannot be extrapolated from the study of individual transcription factors in a different cellular context.
Publication Title
Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compare transcriptomic profiles of human induced pluripotent stem cells (iPSCs), motor neurons (MNs) in vitro differentiated from iPSCs or human ESCs containing a HB9::GFP reporter for MNs, and human fetal spinal cords.
Publication Title
ALS disrupts spinal motor neuron maturation and aging pathways within gene co-expression networks.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We aim to understand the role that Cdx2 plays in specifying the rostro-caudal identity of differentiating motor neurons. We find that expressing Cdx2 in combination with FGF signaling is sufficient to produce motor neurons with a more caudal identity. ChIP-seq analysis of Cdx2 finds that it binds extensively throughout the Hox regions in progenitor motor neurons. Analysis of polycomb-associated chromatin over Hox regions in the subsequently generated motor neurons finds that Cdx2 binding corresponds to chromatin domains encompassing de-repressed caudal Hox genes. These results suggest a direct role for Cdx2 in specifying caudal motor neuron identity.
Publication Title
Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 3 Downloadable Samples
Illumina HiSeq 2000
Description
Human pluripotent stem cells are a promising source of diverse cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons, is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that induce up to 50% motor neurons within 3 weeks from human pluripotent stem cells with defined subtype identities that are relevant to neurodegenerative diseases. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1 and column-specific markers that mirror those observed in vivo in human fetal spinal cord. They also exhibited spontaneous and induced activity, and projected axons towards muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1+/LHX3-). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays. Overall design: We analyzed 3 samples including 2 positive samples and 1 negative sample. Descriptions are as follows: a) Positive Sample 1: SHH-derived, day 21 GFP-high FACS-purified motor neurons. b) Positive Sample 2: S+P-derived, day 21 GFP-high FACS-purified motor neurons. c) Negative: S+P condition, day 21 GFP-off FACS-purified non-motor neurons. Initial analysis of data was performed on ~40% of fastq reads (Amoroso et al., J Neurosci 2013 Jan 9;33(2):574-86. PMID: 23303937). Further processing of the full dataset has since been carried out and the updated rpkm file and expression analysis reflecting all aligned reads can be accessed at: http://scholar.harvard.edu/amorosornaseq/
Publication Title
Accelerated high-yield generation of limb-innervating motor neurons from human stem cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Suz12(Bgal/Bgal) ESCs express a truncated form of Suz12 fused to Beta-galactosidase. These cells maintain a reduced level of H3K27me3 despite this mutation to a core component of PRC2, unlike Eed-/- ESCs whose H3K27me3 is ablated. Overall design: RNA-seq was performed in wild type and Suz12(Bgal/Bgal) ESCs, here used to demonstrate the coverage of the Suz12 gene in mRNA reads.
Publication Title
Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 570 Downloadable Samples
- NextSeq 500
Description
We report the comparative gene expression between embryonic stem cell derived cranial and spinal motor neurons and multiple time points after induction and primary cultured ocular and spinal motor neurons, using single cell RNA sequencing. Overall design: Single neurons were isolated in 96-well plates and their gene expression profiled using SMART-Seq2 from 8 samples: (1-2) primary cultured oculomotor/trochlear motor neurons and spinal motor neurons collected at embryonic day E11.5 and cultured for 7 days, (3-8) ESC-derived induced cranial and spinal motor neurons at either 2 days, 5 days, or 7 days after plating.
Publication Title
Stem cell-derived cranial and spinal motor neurons reveal proteostatic differences between ALS resistant and sensitive motor neurons.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina Genome Analyzer
Description
Alternative splicing (AS) is a key process underlying the expansion of proteomic diversity and the regulation of gene expression. However, the contribution of AS to the control of embryonic stem cell (ESC) pluripotency is not well understood. Here, we identify an evolutionarily conserved ESC-specific AS event that changes the DNA binding preference of the forkhead family transcription factor FOXP1. We show that the ESC-specific isoform of FOXP1 stimulates the expression of transcription factor genes required for pluripotency including OCT4, NANOG, NR5A2 and GDF3, while concomitantly repressing genes required for ESC differentiation. Remarkably, this isoform also promotes the maintenance of ESC pluripotency and the efficient reprogramming of somatic cells to induced pluripotent stem cells. These results thus reveal that an AS switch plays a pivotal role in the regulation of pluripotency and functions by controlling critical ESC-specific transcriptional programs. Overall design: Exons 18 and 18b form a mutually exclusive splicing event. The FOXP1 (non-ES) isoform contains only exon 18 and not 18b, while the FOXP1-ES isoform contains only exon 18b and not 18. To investigate whether FOXP1 and FOXP1-ES control different sets of genes, we performed knockdowns using custom siRNA pools targeting FOXP1 exons 18 or 18b in undifferentiated H9 cells, followed by RNA-Seq profiling.
Publication Title
An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Hmx1 is a transcription factor expressed in the developing eye and ear and in some other parts of the nervous system. Dumbo mice are carrying the Hmx1 p.Q64X loss-of-function mutation (Munroe et al., 2009. BMC Developmental Biology). Transcriptomic analyses of this mouse model allows to decipher biological pathways under the control of Hmx1. In our study, we used it to better understand the role of Hmx1 in the retina and to identify several of its target genes.
Publication Title
Identification of HMX1 target genes: a predictive promoter model approach.
Sample Metadata Fields
No sample metadata fields
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