Project description:There are a total of four samples each for this analysis. Each sample consists of the cells grown on three 10 cm culture plates. Each plate should have 2x106 cells for a total of 6x106 cells per sample when all three plates are combined. The first sample is undifferentiated human embryonic stem cells, the second sample is human glutamatergic neurons derived from those human embryonic stem cells, the third sample is undifferentiated human induced pluripotent stem cells and the fourth sample is human glutamatergic neurons derived from those human induced pluripotent stem cells.
Project description:Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to their developmental potency. Tetraploid complementation, through which an entire organism is produced from donor pluripotent cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs from other species besides mice can pass this test. Here we show that the rat ESCs at very early passages are also capable to produce fertile offspring by tetraploid complementation, however, this capacity is rapidly lost during culture due to the loss of genomic imprinting. Our findings support that the naïve ground state pluripotency exists in rat and can be captured in rat ESCs, yet may be subjected to species-specific regulations, which have implications for the derivation and application of naïve pluripotent stem cells in other species including human.
Project description:Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to their developmental potency. Tetraploid complementation, through which an entire organism is produced from donor pluripotent cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs from other species besides mice can pass this test. Here we show that the rat ESCs at very early passages are also capable to produce fertile offspring by tetraploid complementation, however, this capacity is rapidly lost during culture due to the loss of genomic imprinting. Our findings support that the naïve ground state pluripotency exists in rat and can be captured in rat ESCs, yet may be subjected to species-specific regulations, which have implications for the derivation and application of naïve pluripotent stem cells in other species including human.
Project description:Chavez2009 - a core regulatory network of OCT4 in human embryonic stem cells
A core OCT4-regulated network has been identified as a test case, to analyase stem cell characteristics and cellular differentiation.
This model is described in the article:
In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach.
Chavez L, Bais AS, Vingron M, Lehrach H, Adjaye J, Herwig R
BMC Genomics, 2009, 10:314
Abstract:
BACKGROUND: The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory network governed by the transcription factors OCT4, SOX2 and NANOG. Recent studies on reprogramming somatic cells to induced pluripotent stem cells highlight OCT4 as a key regulator of pluripotency.
RESULTS: We have carried out an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments along with promoter sequence analysis of putative target genes) and identified a core OCT4 regulatory network in human embryonic stem cells consisting of 33 target genes. Enrichment analysis with these target genes revealed that this integrative analysis increases the functional information content by factors of 1.3 - 4.7 compared to the individual studies. In order to identify potential regulatory co-factors of OCT4, we performed a de novo motif analysis. In addition to known validated OCT4 motifs we obtained binding sites similar to motifs recognized by further regulators of pluripotency and development; e.g. the heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC transcriptional activity that leads to cell growth and proliferation.
CONCLUSION: Our analysis shows how heterogeneous functional information can be integrated in order to reconstruct gene regulatory networks. As a test case we identified a core OCT4-regulated network that is important for the analysis of stem cell characteristics and cellular differentiation. Functional information is largely enriched using different experimental results. The de novo motif discovery identified well-known regulators closely connected to the OCT4 network as well as potential new regulators of pluripotency and differentiation. These results provide the basis for further targeted functional studies.
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