Identifying the signals that regulate the survival, lineage allocation and specification of pancreas progenitors will help elucidate the embryonic origins of pancreas dysfunction and provide important cues for the efficient conversion of pluripotent stem cells into fully functional ß cells. Several transcription factors regulating the conversion of the early pancreatic progenitors into terminally differentiated cells have been identified but extracellular signals regulating pancreas development are less well understood. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata and genomics we have found that sphingosine-1-phosphate signalling through plays a key role in this process. S1p signalling stabilizes the Hippo pathway effector YAP to promote progenitor survival, acinar and endocrine specification. Endocrine cell specification relies on Gai subunits revealing an unexpected dependence of lineage specification on selected intracellular signalling components. Independently of YAP stabilization, S1p signalling attenuates Notch levels, thus regulating lineage allocation. These findings identify S1p signalling as a key pathway coordinating cell survival, lineage allocation and specification during pancreas development. Overall design: Analysis was carried out at 14.5 dpc embryonic pancreata and in 14.5 dpc embryonic pancreata that have been cultured in air to liquid interface cultures for two days (14.5 + 2). For the 14.5 dpc analysis wild type (14.5 wt) and S1pr2 null (14.5 S1pr2 null) pancreata were analyzed. For the analysis of cultured embryonic pancreata, conditions used were either standard conditions (14.5 + 2) or in the presence of 15 uM of JTE013 (14.5 + 2 + JTE) or in the presence of 15 uM of JTE013 and 50 ng/ml CTGF (14.5 + 2 + JTE + CTGF). Three biological replicates were used for each stage/condition for a total of 15 samples.
Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling.
Cell line, Subject
View SamplesNHEK cells were plated at a density of 8 x 10 000/cm2 and the cell cultures were grown for 24 hours before addition of 2 mM N-Acetyl-L-Cystein. RNA obtained from cultures grown for 1, 12 and 24 hrs after NAC treatment were compared to RNA from untreated cells at the corresponding time points. I.e 1 hour NAC treated vs 1 hour untreated cells etc. Each EXTRACT represents an individual mRNA extraction and subsequent cDNA synthesis from a batch of totalRNA originating from one cellculture dish.
Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro.
Specimen part, Subject, Compound, Time
View SamplesCaco-2 human colon carcinoma cells were seeded at a density of 9 x 10 000 cells/cm2 and the cell cultures were grown for 24 hours before addition of 10 mM N-Acetyl-L-Cystein. RNA obtained from cultures grown for 1, 12 and 24 hrs after NAC treatment were compared to RNA from untreated cells at the corresponding time points. I.e 1 hour NAC treated vs 1 hour untreated cells etc. Each "SAMPLE" represents a biological replicate (i.e. separate cellcultures treated similarily) although I have given identical SAMPLE numbers in pairs.
Global gene expression analysis in time series following N-acetyl L-cysteine induced epithelial differentiation of human normal and cancer cells in vitro.
Specimen part, Cell line, Subject, Compound, Time
View SamplesWe studied the KRAS and NRAS mutational status in pediatric MLL-AF4+ leukemia patients by means of ultra deep amplicon sequencing. The gene expression profiles of RAS wild type and RAS mutated patients were investigated by gene expression analysis. We showed that mutated patients were characterized by a RAS related expression signature.
Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.
Specimen part, Disease, Disease stage, Subject
View SamplesTo gain insight into the etiopathogenesis of Multiple sclerosis (MS) we investigated gene expression changes in CD4+ and CD8+ T lymphocytes from monozygotic twins (MZ) discordant for relapsing remitting MS.
CD161(high)CD8+T cells bear pathogenetic potential in multiple sclerosis.
Specimen part, Disease, Disease stage
View SamplesA widely shared view reads that 'MSCs' are ubiquitous in human connective tissues, can be defined by a common in vitro phenotype, share a skeletogenic potential as assessed by in vitro differentiation assays, and coincide with the ubiquitous 'pericytes.' Using stringent in vivo differentiation assays and transcriptome analysis, we show here that human cell populations from different anatomical sources, which would all be regarded as 'MSCs' based on these criteria and assumptions, actually differ widely in their transcriptomic signature and in vivo differentiation potential. In contrast, they share the capacity to guide the assembly of functional microvessels in vivo, regardless of their anatomical source, or in situ identity as perivascular or circulating cells. This analysis further reveals that muscle 'pericytes,' which are not spontaneously osteo-chondrogenic as previously claimed, may indeed coincide with an ectopic perivascular subset of committed myogenic cells similar to satellite cells. Cord blood-derived stromal cells, on the other hand, display the unique capacity to form cartilage in vivo spontaneously, in addition to an assayable osteogenic capacity. These data suggest the need to revise current misconceptions on the origin and function of so-called 'MSCs,' with important applicative implications. The data also support the view that rather than a uniform class of 'MSCs,' different mesoderm derivatives include distinct classes of tissue-specific committed progenitors, likely of different developmental origin.
No Identical "Mesenchymal Stem Cells" at Different Times and Sites: Human Committed Progenitors of Distinct Origin and Differentiation Potential Are Incorporated as Adventitial Cells in Microvessels.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150.
No sample metadata fields
View SamplesWe compare the transcriptome of two different clones of multipotent adult progenitor cells (MAPCs) using Affymetrix arrays.
Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells.
No sample metadata fields
View SamplesGene expression of Double Positive, and Single Positive CD4+ human thymocytes
Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150.
No sample metadata fields
View SamplesCaspases, proteolytic enzymes involved in cell death could play a role independent of cell death in the developing heart
Executioner Caspase-3 and 7 Deficiency Reduces Myocyte Number in the Developing Mouse Heart.
Age, Specimen part
View Samples