Project description:This SuperSeries is composed of the following subset Series: GSE28669: Identification of Sox9-Regulated Pathways During Early Pancreas Organogenesis GSE28670: Identification of Sox9-Regulated Pathways During the Secondary Transition Stage of Pancreas Development Refer to individual Series
Project description:Sox9 target genes were identified during the secondary transition stage of pancreas development by comparing gene expression in Sox9-ablated versus wild-type pancreata using microarray analysis.
Project description:Sox9 target genes were identified during the secondary transition stage of pancreas development by comparing gene expression in Sox9-ablated versus wild-type pancreata using microarray analysis. Sox9 was conditionally ablated during the secondary transition in the developing pancreas via recombination of a Sox9-flox allele (Kist et al., 2002) using the tamoxifen-inducible Rosa26-CreER allele (Vooijs et al., 2001). Dams were injected with 6 mg/40 g tamoxifen in corn oil at e12.5. Pancreata were manually microdissected at e15.5. Total RNA was isolated and pooled from pancreata of e15.5 Sox9fl/fl; Rosa26-CreER (mutant) versus Rosa26-CreER (wild-type) littermates for four biological replicates.
Project description:Development of the pancreas from the endoderm is initiated at embryonic day 9 of mouse development and over the following days several different cell types develop from pancreas progenitor cells. A distinct phase of pancreas development, known as the secondary transition, is initiated at day 13 of development and one of the key features of this transition is a massive increase in the number of mature endocrine cells. To study gene expression in pancreas during the secondary transition we performed high-density oligonucleotide microarray experiments on dorsal pancreas tissue isolated from NMRI embryos on consecutive days from e12.5 to e16.5. Keywords: time course
Project description:Development of the pancreas from the endoderm is initiated at embryonic day 9 of mouse development and over the following days several different cell types develop from pancreas progenitor cells. A distinct phase of pancreas development, known as the secondary transition, is initiated at day 13 of development and one of the key features of this transition is a massive increase in the number of mature endocrine cells. To study gene expression in pancreas during the secondary transition we performed high-density oligonucleotide microarray experiments on dorsal pancreas tissue isolated from NMRI embryos on consecutive days from e12.5 to e16.5. Experiment Overall Design: Dorsal pancreata were isolated from embryos at embryonic day 12.5, 13.5, 14.5, 15.5, and 16.5 and pooled litter-wise prior to total RNA extraction. From each pool, two independent labelling reactions were made, and each sample was hybridized to the entire Murine Genome U74 version 2 chip set (A, B, and C).
Project description:Genes specific to Sox9+ pancreatic progenitors were identified by comparing the gene expression in embryonic and adult Sox9+ cells. We used microarray analysis to detail the global changes in gene expression as Sox9 positive embryonic pancreatic progenitors differentiatiate into adult ductal cells or the endocrine lineage. GFP positive cells from Sox9-EGFP mouse pancreas were isolated by FACS at different stages of development (e10.5, e15.5, and p23) for RNA extraction and hybridization to Affymetrix microarrays. To obtain populations highly enriched in Sox9 expression, we collected only GFP Hi populations for analysis. To identify gene expression changes specific to the differentiation of progenitors to ductal cells or endocrine cells, we also isolated and analyzed the gene expression profile of GFP negative cells isolated at p23, as well as GFP positive cells isolated from Ngn3-EGFP mouse pancreas at e15.5. These two populations allow the identification of genes whose expression is associated with the newly differentiated endocrine progeny in the embryo (Ngn3-GFP positive) and adult acinar and endocrine cells at p23.
Project description:The genomic regulatory programs that underlie human organogenesis are poorly understood. Human pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer, and diabetes. We have now created maps of transcripts, active enhancers, and transcription factor networks in pancreatic multipotent progenitors obtained from human embryos, or derived in vitro from human embryonic stem cells. This revealed that artificial progenitors recapitulate salient transcriptional and epigenomic features of their natural counterparts. Using this resource, we show that TEAD1, a transcription factor controlled by Hippo signaling, is a core component of the combinatorial code of pancreatic progenitor enhancers. TEAD thus activates genes encoding regulators of signaling pathways and stage-specific transcription factors that are essential for normal pancreas development. Accordingly, chemical and genetic perturbations of TEAD and its coactivator YAP inhibited expression of known regulators such as FGFR2 and SOX9, and suppressed the proliferation and expansion of mouse and zebrafish pancreatic progenitors. These findings provide a resource of active enhancers and transcripts in human pancreatic multipotent progenitors, and uncover a central role of TEAD and YAP as signal-responsive regulators of the transcriptional program of early pancreas development.