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GSE59865
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The differentiated state of somatic cells provides barriers for the efficient derivation of induced pluripotent stem cells (iPSCs). To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. This revealed that inhibition of TGF together with activation of Wnt signaling in presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after one week of reprogramming factor expression. In contrast, hepatic progenitors and blood progenitors predominantly required only TGF inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner. We further demonstrate that expression of specific chromatin-modifying enzymes and reduced TGF/MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Together, our observations define novel cell type-specific requirements for the rapid and synchronous reprogramming of somatic cells.
Publication Title
Combinatorial modulation of signaling pathways reveals cell-type-specific requirements for highly efficient and synchronous iPSC reprogramming.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 61 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 57 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
Induced pluripotent stem cells (iPSCs) can be generated by enforced expression of defined transcription factors in somatic cells. It remains controversial whether iPSCs are equivalent to blastocyst-derived embryonic stem cells (ESCs). Using genetically matched cells, we found that the overall mRNA expression patterns of these cell types are indistinguishable with the exception of a few transcripts encoded on chromosome 12qF1.
Publication Title
Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2000
Description
Herein, we demonstrated that the cell lineage commitment is unexpectedly regulated by the novel functions of H2A.X, a histone variant which was only well-known for its role in genome integrity maintenance previously. Surprisingly, only in ESCs but not differentiated cells, H2A.X is specifically targeted to genomic regions encoding early embryonic and extra-embryonic lineage genes to repress their expression. In addition, H2A.X is also enriched at genomic regions sensitive to replication stress and maintains genomic stability thereat. Most interestingly, faithful H2A.X deposition plays critical roles in maintaining both cell lineage commitment and genome integrity in iPSC. In iPSC lines which support the development of "all-iPS" animals, H2A.X deposition faithfully recapitulates the ESC pattern and therefore, the genome stability and cell lineage commitment are maintained. In iPSC lines that fail to support embryonic development, defective H2A.X depositions result in aberrant upregulation of early embryonic and extra-embryonic lineage genes and H2A.X-dependent genome instability. Overall design: mRNA-Seq of WT ESC and H2A.X KO ESC; and 4N+, 4N- iPSC.
Publication Title
Histone variant H2A.X deposition pattern serves as a functional epigenetic mark for distinguishing the developmental potentials of iPSCs.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Pluripotent cells can be derived from somatic cells by either overexpression of defined transcription factors (resulting in induced pluripotent stem cells (iPSCs)) or by nuclear transfer or cloning (resulting in NT-ESCs). To determine whether cloning further reprograms iPSCs, we used iPSCs as donor cells in nuclear transfer experiments.
Publication Title
Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- IlluminaHiSeq2000
Description
In this experiment, we sought to determine how PRDM14 and CBFA2T2 regulate the transcriptome of mouse embryonic stem cells Overall design: 3 KO mESC lines with 3 biological replicates for each (wild type (3), PRDM14-KO (3), CBFA2T2 (3))
Publication Title
Co-repressor CBFA2T2 regulates pluripotency and germline development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Mouse ES cells were stably transduced with a lentivirus expressing either wild-type KBP or the stable mutant KBP(KK/RR) and maintained in self-renewing growth conditions. RNA-seq was performed to assess mRNA expression differences caused by the stabilization of KBP. Overall design: 6 samples [a triplicate set for ES cells expressing wild-type KBP and a triplicate set expressing KBP(KK/RR)] were analyzed.
Publication Title
The TDH-GCN5L1-Fbxo15-KBP axis limits mitochondrial biogenesis in mouse embryonic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The generation of induced pluripotent stem cells (iPSCs) often results in aberrant silencing of the imprinted Dlk1-Dio3 gene cluster, which compromises their ability to generate entirely iPSC-derived mice (all-iPSC mice). Here, we show that reprogramming in the presence of ascorbic acid attenuates hypermethylation of Dlk1-Dio3 by enabling a chromatin configuration at its imprint control region that interferes with abnormal binding of the DNA methyltransferase Dnmt3a. This approach allowed us to generate adult all-iPSC mice from mature B cells, which have thus far failed to support the development of exclusively iPSC-derived postnatal mice. Our data demonstrate that factor-mediated reprogramming can endow a defined, terminally differentiated cell type with a developmental potential equivalent to that of embryonic stem cells. More generally, these findings indicate that the choice of culture conditions used for transcription factor-mediated reprogramming can strongly influence the epigenetic and biological properties of resultant iPSCs.
Publication Title
Ascorbic acid prevents loss of Dlk1-Dio3 imprinting and facilitates generation of all-iPS cell mice from terminally differentiated B cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 45 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Induced pluripotent stem cells (iPSCs) have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPSCs generated from different cell types are molecularly and functionally similar.
Publication Title
Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Induced pluripotent stem (iPS) cells have been derived from various somatic cell populations through ectopic expression of defined factors. It remains unclear whether iPS cells generated from different cell types are molecularly and functionally similar. Here, we show that iPS cells obtained from fibroblasts, hematopoietic and myogenic cells exhibit distinct transcriptional and epigenetic patterns. Moreover, we demonstrate that cellular origin influences the in vitro differentiation potentials of iPS cells into embryoid bodies and different hematopoietic cells. Our results suggest that low-passage iPS cells retain a transient epigenetic memory of their somatic cells of origin, which manifests as differential gene expression and altered differentiation capacity. These observations might affect ongoing attempts to use iPS cells for disease modeling and also could be exploited for potential therapeutic applications to enhance differentiation into desired cell lineages.
Publication Title
Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples