Filters
Technology
Platform
GSE44972
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcription factor (TF)-induced reprogramming of somatic cells into induced pluripotent stem cells (iPSC) is associated with genome-wide changes in chromatin modifications. Polycomb-mediated histone H3 lysine-27 trimethylation (H3K27me3) has been proposed as a defining mark that distinguishes the somatic from the iPSC epigenome. Here, we dissected the functional role of H3K27me3 in TF-induced reprogramming through the inactivation of the H3K27 methylase EZH2 at the onset of reprogramming. Our results demonstrate that surprisingly the establishment of functional iPSC proceeds despite global loss of H3K27me3. iPSC lacking EZH2 efficiently silenced the somatic transcriptome and differentiated into tissues derived from the three germ layers. Remarkably, the genome-wide analysis of H3K27me3 in Ezh2 mutant iPSC cells revealed the retention of this mark on a highly selected group of Polycomb targets enriched for developmental regulators controlling the expression of lineage specific genes. Erasure of H3K27me3 from these targets led to a striking impairment in TF-induced reprogramming. These results indicate that PRC2-mediated H3K27 trimethylation is required on a highly selective core of Polycomb targets whose repression enables TF-dependent cell reprogramming.
Publication Title
Cell reprogramming requires silencing of a core subset of polycomb targets.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A catalytic role has been proposed in neoplastic angiogenesis and cancer progression for bone marrow-derived endothelial progenitor cells (EPCs). However, in preclinical and clinical studies the quantitative role of marrow-derived EPCs in cancer vascularization was found to be extremely variable. Adipose tissue represents an attractive source of autologous adult stem cells due to its abundance and surgical accessibility. CD34+cells from Lipotransfer aspirates (LAs) of patients undergoing breast reconstruction after breast cancer surgery were compared with CD34+ cells from Leucapheresis of normal subjects.
Publication Title
The white adipose tissue used in lipotransfer procedures is a rich reservoir of CD34+ progenitors able to promote cancer progression.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Human adipose tissue contains two populations of progenitors (EPCs and ASCs) with cooperative roles in breast cancer. EPCs (CD45-CD34+CD31+CD13-CCRL2+) can generate endothelial cells. ASCs (CD45-CD34+CD31-CD13+CD140b+) are mesenchymal progenitors which generated pericytes.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Polycomb proteins control proliferation and cellular transformation regulating DNA replication independently of cell cycle checkpoints
Publication Title
Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
O-linked N-acetylglucosamine (O-GlcNAc ) transferase (OGT) activity is essential for embryonic stem (ES) cell viability and mouse development. OGT is present in both cytoplasm and nucleus of different cell types and mediates serine or threonine glycosylation. The Ogt gene locus resides on the X-chromosome and its activity is required for the viability of male ES cells. Using Ogt conditional knock out (KO) ES cells it was shown the failure of establishing stable KO ES clones further suggesting that Ogt activity is required for ES cell self-renewal and pluripotency. For understanding these changes, we performed global gene expression upon silencing of Ogt mediated by esiRNA in mouse Embryonic Stem Cells.
Publication Title
Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
In order to identify genes regulated by VE-cadherin expression, we compared a mouse VE-cadherin null cell line (VEC null) with the same line reconstituted with VE-cadherin wild type cDNA (VEC positive). The morphological and functional properties of these cell lines were described previously [Lampugnani,M.G. et al. Contact inhibition of VEGF-induced proliferation requires vascular endothelial cadherin, beta-catenin, and the phosphatase DEP-1/CD148. J. Cell Biol. 161, 793-804 (2003)]. By Affymetrix gene expression analysis we found several genes up-regulated by VE-cadherin, among which claudin-5 reached remarkably high levels. The up-regulation of these genes required not only VE-cadherin expression but also cell confluence suggesting that VE-cadherin clustering at junctions was needed.
Publication Title
Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Endothelial cells (ECs) express two members of the cadherin family, VE- and N-cadherin. While VE-cadherin induces EC homotypic adhesion, N-cadherin function in ECs remains largely unknown. EC-specific inactivation of either VE- or N-cadherin leads to early foetal lethality suggesting that these cadherins play a non-redundant role in vascular development.
Publication Title
Overlapping and divergent signaling pathways of N-cadherin and VE-cadherin in endothelial cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 15 Downloadable Samples
Illumina HiSeq 2000, Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
7q11.23 dosage-dependent dysregulation in human pluripotent stem cells affects transcriptional programs in disease-relevant lineages.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
We apply the cellular reprogramming experimental paradigm to two disorders caused by symmetrical copy number variations (CNV) of 7q11.23 and displaying a striking combination of shared as well as symmetrically opposite phenotypes: Williams Beuren syndrome (WBS) and 7q microduplication syndrome (7dup). Through a uniquely large and informative cohort of transgene-free patient-derived induced pluripotent stem cells (iPSC), along with their differentiated derivatives, we find that 7q11.23 CNV disrupt transcriptional circuits in disease-relevant pathways already at the pluripotent state. These alterations are then selectively amplified upon differentiation into disease-relevant lineages, thereby establishing the value of large iPSC cohorts in the elucidation of disease-relevant developmental pathways. In addition, we functionally define the quota of transcriptional dysregulation specifically caused by dosage imbalances in GTF2I (also known as TFII-I), a transcription factor in 7q11.23 thought to play a critical role in the two conditions, which we found associated to key repressive chromatin modifiers. Finally, we created an open-access web-based platform (accessible at http://bio.ieo.eu/wbs/ ) to make accessible our multi-layered datasets and integrate contributions by the entire community working on the molecular dissection of the 7q11.23 syndromes.
Publication Title
7q11.23 dosage-dependent dysregulation in human pluripotent stem cells affects transcriptional programs in disease-relevant lineages.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples