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GSE28811
Mus musculus
37 Downloadable Samples
Illumina mouseRef-8 v1.1 expression beadchip
Description
Although nuclear transfer allows the reprogramming of somatic cells to totipotency, little is known concerning the kinetics by which it takes place or the minimum requirements for its success. Here, we demonstrate that reprogramming can be achieved within a few hours and a single cell-cycle as long as two key constraints on reprogramming are satisfied. First, the recipient cell chromosomes must be removed during mitosis. Second, the nuclear envelope of the donor cell must be broken down and its chromosomes condensed, allowing an embryonic nucleus to be constructed around the incoming chromosomes. If these requirements are not met, then reprogramming fails and embryonic development arrests. These results point to a central role for processes intimately linked to cell division in mediating efficient transitions between transcriptional programs.
Publication Title
Reprogramming within hours following nuclear transfer into mouse but not human zygotes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina mouseRef-8 v1.1 expression beadchip
Description
Analysis of iPS cells generated with a small molecule, RepSox (RS), as well as a time-course of gene expression changes in cells treated with RS.
Publication Title
A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
Illumina HiSeq 1500
Description
Seckel syndrome (SS) is a rare spectrum of congenital severe microcephaly and dwarfism. One SS-causative gene is Ataxia Telangiectasia and Rad3-Related Protein (ATR), and ATR (c.2101 A>G) mutation causes skipping of exon 9, resulting in a hypomorphic ATR defect in patients. Because ATR governs DNA repair response, the mutation has been considered the cause of an impaired response to DNA replication stress in neuronal progenitor cells (NPCs), which is associated with the pathogenesis of microcephaly. However, the precise mechanism through which the mutation causes SS remains unclear. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts carrying the ATR mutation and an isogenic ATR-corrected counterpart iPSC clone by genome editing. Interestingly, SS-patient-derived iPSCs (SS-iPSCs) exhibited cell type-specific splicing; exon 9 was dominantly skipped in fibroblasts and iPSC-derived NPCs, but it was included in undifferentiated iPSCs and definitive endodermal cells. SS-iPSC-derived NPCs (SS-NPCs) showed distinct expression profiles from ATR non-mutated NPCs. In SS-NPCs, abnormal mitotic spindles were observed more frequently than in gene-corrected counterparts, and the alignment of NPCs in the surface of the neurospheres was perturbed. Finally, we tested several splicing-modifying compounds and found that a CLK1 inhibitor, TG003, could pharmacologically rescue the exon 9 skipping in SS-NPCs. Furthermore, treatment with TG003 restored the function of ATR in SS-NPCs and decreased the frequency of abnormal mitotic events. In conclusion, our iPSC model of SS revealed a novel function of the ATR mutation in NPCs and NPC-specific missplicing, proving its usefulness for dissecting the pathophysiology of ATR-SS. Overall design: RNA-sequencing was conducted to identify the transcriptomic profiling of iPSC-derived cells
Publication Title
Verification and rectification of cell type-specific splicing of a Seckel syndrome-associated ATR mutation using iPS cell model.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Loss of CLP1 activity results in the accumulation of novel sets of small RNA fragments derived from aberrant processing of tyrosine pre-tRNA. Such tRNA fragments sensitize cells to oxidative stress-induced p53 activation and p53-dependent cell death. Overall design: 2 samples, Wt and Clp1(k/k), no replicates
Publication Title
CLP1 links tRNA metabolism to progressive motor-neuron loss.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 1500
Description
mRNA sequencing analysis of FACS-purified leptotene/zygotene (L/Z) spermatocytes Overall design: Compare transcriptomes of WT, Pld6 KO, and Dnmt3l KO germ cells in the F1 hybrid background of B6 and MSM to study these mutations affecting gene expression due to nearby retrotransposons.
Publication Title
Switching of dominant retrotransposon silencing strategies from posttranscriptional to transcriptional mechanisms during male germ-cell development in mice.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Liver RNA samples from C57BL6 mice drinking Hydrogen water for 4 weeks
Publication Title
Molecular hydrogen upregulates heat shock response and collagen biosynthesis, and downregulates cell cycles: meta-analyses of gene expression profiles.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Common myeloid progenitor cells from murine bone marrow were sorted according to ROS content using FACS with H2-DCFDA staining.
Publication Title
Intracellular reactive oxygen species mark and influence the megakaryocyte-erythrocyte progenitor fate of common myeloid progenitors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
It remains controversial whether human induced pluripotent stem cells (hiPSCs) are distinct from human embryonic stem cells (hESCs) in their molecular signatures and differentiation properties. We examined the gene expression and DNA methylation of 49 hiPSC and 10 hESC lines and identified no molecular signatures that distinguished hiPSCs from hESCs. Comparisons of the in vitro directed neural differentiation of 40 hiPSC and four hESC lines showed that most hiPSC clones were comparable to hESCs. However, in seven hiPSC clones, significant amount of undifferentiated cells persisted even after neural differentiation and resulted in teratoma formation when transplantated into mouse brains. These differentiation-defective hiPSC clones were marked by higher expression of several genes, including those expressed from long terminal repeats of human endogenous retroviruses. These data demonstrated that many hiPSC clones are indistinguishable from hESCs, while some defective hiPSC clones need to be eliminated prior to their application for regenerative medicine.
Publication Title
Differentiation-defective phenotypes revealed by large-scale analyses of human pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- IlluminaHiSeq2000
Description
Although many distinct mutations in a variety of genes are known to cause Amyotrophic Lateral Sclerosis (ALS), it remains poorly understood how they selectively impact motor neuron biology and whether they converge on common pathways to cause neural degeneration. Here, we have combined reprogramming and stem cell differentiation approaches with genome engineering and RNA sequencing to define the transcriptional changes that are induced in human motor neurons by mutant SOD1. Mutant SOD1 protein induced a transcriptional signature indicative of increased oxidative stress, reduced mitochondrial function, altered sub-cellular transport as well as activation of the ER stress and unfolded protein response pathways. Functional studies demonstrated that perturbations in these pathways were indeed the source of altered transcript levels. Overall design: 5 samples, 2 patient-derived SOD1A4V and 3 isogenic control samples where the mutation has been corrected. All samples are motor neurons derived from induced pluripotent stem cells (iPSCs), and isolated after lentiviral infection with an Hb9:RFP construct and FACS purification. Each sample is a separate biological replicate.
Publication Title
Pathways disrupted in human ALS motor neurons identified through genetic correction of mutant SOD1.
Sample Metadata Fields
No sample metadata fields
View Samples