Stem cell development requires selection of specific genetic programs to direct cellular fate. Using microarray technology, we profile expression trends at selected timepoints during stem cell differentiation to characterize these changes.
Genomic chart guiding embryonic stem cell cardiopoiesis.
Specimen part
View SamplesThe objective of this study was the assessment of transcriptional dysregulation in particular with regard to B-cell differentiation factors. Most studies focus on cross-section analyses of various leukemia subtypes to identify differentially regulated genes lacking suitable reference models. Here we applied comparative intraindividual transcriptome analysis of B-precursor ALL of childhood, which introduces a side-by-side analysis of leukemic cells and matched normal lymphoblasts from the same individual in complete continuous remission after the end of re-induction therapy. This approach reduces noise by eliminating interindividual variability.
Aberrant ZNF423 impedes B cell differentiation and is linked to adverse outcome of ETV6-RUNX1 negative B precursor acute lymphoblastic leukemia.
Specimen part, Subject
View Samplesgamma delta intraepithelial lymphocytes were isolated from the colons of DSS-treated and untreated mice. Total RNAs were isolated and compared by Affymetrix DNA microarray.
Reciprocal interactions between commensal bacteria and gamma delta intraepithelial lymphocytes during mucosal injury.
No sample metadata fields
View SamplesThe goal of the microarray experiment was to do a head-to-head comparison of the U1 Adaptor technology with siRNA in terms of specificity at the genome-wide level. U1 Adaptors represent a novel gene silencing method that employs a mechanism of action distinct from antisense and RNA interference (RNAi). The U1 Adaptor is a bifunctional oligonucleotide having a Target Domain that is complementary to a site in the target gene's terminal exon and a U1 Domain that binds to the U1 small nuclear RNA (snRNA) component of the U1 small nuclear ribonucleoprotein (U1 snRNP) splicing factor. Tethering of U1 snRNP to the target pre-mRNA inhibits 3' end processing (i.e., polyA tail addition) leading to degradation of that RNA species within the nucleus thereby reducing mRNA levels. We demonstrate that U1 Adaptors can specifically inhibit both reporter and endogenous genes. Further, targeting the same gene either with multiple U1 Adaptors or with U1 Adaptors and small interfering RNAs (siRNAs), strongly enhances gene silencing, the latter as predicted from their distinct mechanisms of action. Such combinatorial targeting requires lower amounts of oligonucleotides to achieve potent silencing.
Gene silencing by synthetic U1 adaptors.
No sample metadata fields
View SamplesThe adult pancreas is capable of limited regeneration after injury, but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into -cells. The induced -cells resemble islet -cells in morphology and histology, express genes essential for -cell function, and release insulin upon glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type.
Loss of Fbw7 reprograms adult pancreatic ductal cells into α, δ, and β cells.
Specimen part, Treatment
View SamplesBy employing FOXA2-deficient mouse models coupled with LIF repletion, we reveal definitive roles of uterine glands in pregnancy establishment.These studies provide original evidence that uterine glands synchronize embryo-endometrial interactions, coordinate on-time embryo implantation, and impact stromal cell decidualization, thereby ensuring embryo viability, placental growth, and pregnancy success. Overall design: Uterine transcriptomes of control and Foxa2-deficient mice were generated on gestational day (GD) 4 and GD 6 following LIF-repletion. All time points were done in quadruplicates.
Uterine glands coordinate on-time embryo implantation and impact endometrial decidualization for pregnancy success.
Specimen part, Cell line, Subject
View SamplesThis study delineated how small intestinal resident microflora impact gene expression in Paneth cells.
Symbiotic bacteria direct expression of an intestinal bactericidal lectin.
No sample metadata fields
View SamplesThe goal of this study was to identify potential AMH-induced genes and regulatory networks controlling regression by RNA-Seq transcriptome analysis of differences in Müllerian Duct mesenchyme between males (AMH signaling on) and females (AMH signaling off) in purified fetal Müllerian Duct mesenchymal cells. This analysis found 82 genes up-regulated in males during MD regression and identified Osterix (Osx)/Sp7, a key transcriptional regulator of osteoblast differentiation and bone formation, as a novel downstream effector of AMH signaling during MD regression. Overall design: Müllerian Duct mesenchymal cells mRNA profiles from 2-7 embryonic day 14.5 embryos were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.
<i>Osterix</i> functions downstream of anti-Müllerian hormone signaling to regulate Müllerian duct regression.
Sex, Specimen part, Cell line, Subject
View SamplesThe Lim1 gene has essential functions during several stages of kidney development. In particular, a tissue specific knockout in the early metanephric mesenchyme results in the formation of the earliest nephron precursor, the renal vesicle, but failure of this structure to progress to the next stage, the comma shaped body. To better understand the molecular nature of this developmental arrest we used a laser capture microdissection-microarray strategy to examine the perturbed gene expression pattern of the mutant renal vesicles. Among the genes found differently expressed were Chrdl2, an inhibitor of BMP signaling, the pro-apoptotic factor Bmf, as well as myob5, an atypical myosin which modulates chemokine and transferring signaling, and pdgfr1, which is important in epithelial folding. Of particular interest, the microarray data indicated that the Dkk1 gene, which encodes an inhibitor of Wnt signaling, was downregulated nine fold in mutants. This was confirmed by in situ hybridizations. It is interesting to note that Lim1 and Dkk1 mutant mice have striking similarities in phenotype. These results suggest that the Dkk1 gene might be a key downstream effector of Lim1 function.
Laser capture-microarray analysis of Lim1 mutant kidney development.
No sample metadata fields
View SamplesBACKGROUND: Lim1 is a homeobox gene that is essential for nephrogenesis. During metanephric kidney development, Lim1 is expressed in the nephric duct, ureteric buds, and the induced metanephric mesenchyme. Conditional ablation of Lim1 in the metanephric mesenchyme blocks the formation of nephrons at the nephric vesicle stage, leading to the production of small, non-functional kidneys that lack nephrons.
Gene expression profiles in developing nephrons using Lim1 metanephric mesenchyme-specific conditional mutant mice.
No sample metadata fields
View Samples