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GSE40335
Mus musculus
30 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A number of key regulators of mouse embryonic stem (ES) cell identity, including the transcription factor Nanog, show strong expression fluctuations at the single cell level. The molecular basis for these fluctuations is unknown. Here we used a genetic complementation strategy to investigate expression changes during transient periods of Nanog downregulation. Employing an integrated approach, that includes high-throughput single cell transcriptional profiling and mathematical modelling, we found that early molecular changes subsequent to Nanog loss are stochastic and reversible. However, analysis also revealed that Nanog loss severely compromises the self-sustaining feedback structure of the ES cell regulatory network. Consequently, these nascent changes soon become consolidated to committed fate decisions in the prolonged absence of Nanog. Consistent with this, we found that exogenous regulation of Nanog-dependent feedback control mechanisms produced more a homogeneous ES cell population. Taken together our results indicate that Nanog-dependent feedback loops play a role in controlling both ES cell fate decisions and population variability.
Publication Title
Nanog-dependent feedback loops regulate murine embryonic stem cell heterogeneity.
Sample Metadata Fields
Specimen part
View Samples- 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- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human oocytes reprogram somatic cells to a pluripotent state.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Gene expression of sibling human ES cell lines are more similar to each other than unrelated cell lines.
Publication Title
Optimal timing of inner cell mass isolation increases the efficiency of human embryonic stem cell derivation and allows generation of sibling cell lines.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
The exchange of the oocyte's genome with the genome of a somatic cell, followed by the derivation of pluripotent stem cells, could enable the generation of specific cell types affected in degenerative human diseases. Such cells, carrying the patient's genome, might be useful for cell replacement. Here we report that the development of human oocytes activated after genome exchange invariably arrests at the late cleavage stages in association with transcriptional abnormalities. In contrast, if the oocyte genome is not removed and the somatic cell genome is merely added, they efficiently develop to the blastocyst stage. Human stem cell lines derived from these blastocysts differentiate into cell types of all three germ layers, and a pluripotent gene expression program is established on the genome derived from the somatic cell. This result demonstrates the feasibility of reprogramming human cells using oocytes and identifies the removal of the oocyte genome as the primary cause of developmental failure after genome exchange. Future work should focus on the critical elements that are associated with the human oocyte genome.
Publication Title
Human oocytes reprogram somatic cells to a pluripotent state.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
The exchange of the oocytes genome with the genome of a somatic cell, followed by the derivation of pluripotent stem cells, could enable the generation of specific cell types affected in degenerative human diseases. Such cells, carrying the patients genome, might be useful for cell replacement. Here we report that the development of human oocytes activated after genome exchange invariably arrests at the late cleavage stages in association with transcriptional abnormalities. In contrast, if the oocyte genome is not removed and the somatic cell genome is merely added, they efficiently develop to the blastocyst stage. Human stem cell lines derived from these blastocysts differentiate into cell types of all three germ layers, and a pluripotent gene expression program is established on the genome derived from the somatic cell. This result demonstrates the feasibility of reprogramming human cells using oocytes and identifies the removal of the oocyte genome as the primary cause of developmental failure after genome exchange. Future work should focus on the critical elements that are associated with the human oocyte genome.
Publication Title
Human oocytes reprogram somatic cells to a pluripotent state.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 83 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The organs of multicellular species are comprised of cell types that must function together to perform specific tasks. One critical organ function is responding to internal or external change but little is known about how responses are tailored to specific cell types or coordinated among them on a global level. Here we use cellular profiling of five Arabidopsis root cell types in response to a limiting resource, nitrogen, to uncover a vast and predominantly cell-specific response that was largely undetectable using traditional methods. These methods reveal a new class of cell-specific nitrogen responses. As a proof-of-principle, we dissected one cell-specific response circuit that mediates nitrogen-induced changes in root branching from pericycle cells. Thus, cellular response profiling links gene modules to discrete functions in specific cell types.
Publication Title
Cell-specific nitrogen responses mediate developmental plasticity.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 45 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
To identify potential transient interactions between a TF and its targets, we developed an approach that can identify primary targets based either on TF-induced regulation or TF-binding, assayed in the same samples. Our studies focused on the TF bZIP1 (BASIC LEUCINE ZIPPER 1), a central integrator of cellular and metabolic signaling.
Publication Title
Hit-and-run transcriptional control by bZIP1 mediates rapid nutrient signaling in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 44 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Densely ionizing radiation is a major component of the space radiation environment and has potentially greater carcinogenic effect compared to sparsely ionizing radiation that is prevalent in the terrestrial environment. It is unknown to what extent the irradiated microenvironment contributes to the differential carcinogenic potential of densely ionizing radiation. To address this gap, 10-week old BALB/c mice were irradiated with 100 cGy sparsely ionizing g-radiation or 10, 30, or 80 cGy of densely ionizing, 350 MeV/amu Si particles and transplanted 3 days later with syngeneic Trp53 null mammary fragments. Tumor appearance was monitored for 600 days. Tumors arising in Si-particle irradiated mice had a shorter median time to appearance, grew faster and were more likely to metastasize. Most tumors arising in sham-irradiated mice were ER-positive, pseudo-glandular and contained both basal keratin 14 and luminal keratin 8/18 cells (designated K14/18), while most tumors arising in irradiated hosts were K8/18 positive (designated K18) and ER negative. Comparison of K18 vs K14/18 tumor expression profiles showed that genes increased in K18 tumors were associated with ERBB2 and KRAS while decreased genes overlapped with those down regulated in metastasis and by loss of E-cadherin. Consistent with this, K18 tumors grew faster than K14/18 tumors and more mice with K18 tumors developed lung metastases compared to mice with K14/18 tumors. However, K18 tumors arising in Si-particle irradiated mice grew even faster and were more metastatic compared to control mice. A K18 Si-irradiated host profile was enriched in genes involved in mammary stem cells, stroma, and Notch signaling. Thus systemic responses to densely ionizing radiation enriches for a ER-negative, K18-positive tumor, whose biology is more aggressive compared to similar tumors arising in non-irradiated hosts.
Publication Title
Densely ionizing radiation acts via the microenvironment to promote aggressive Trp53-null mammary carcinomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 42 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Root branching in response to changes in nitrogen status in the soil, is a dramatic example of the plants remarkable developmental plasticity. In recent work we investigated the genetic architecture of developmental plasticity, combining phenoclustering and genome-wide association studies in 96 Arabidopsis thaliana ecotypes with expression profiling in 7 ecotypes, to characterise natural variation in root architectural plasticity at the phenotypic, genetic, and transcriptional levels. This series contains the microarray expression data for 7 ecotypes that represent a range of root branching strategies.
Publication Title
No associated publication
Sample Metadata Fields
Age, Specimen part
View Samples