Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Identification of Sox9-Regulated Pathways During Early Pancreas Organogenesis

ABSTRACT: Sox9 target genes were identified by comparing gene expression in Sox9-ablated versus wild-type pancreata using microarray analysis. Sox9 was conditionally ablated in the developing pancreas via recombination of a Sox9-flox allele (Kist et al., 2002) using the Pdx1-Cre transgene (Gu et al., 2002). Total RNA was isolated and pooled from dorsal pancreatic epithelia of e12.5 Sox9fl/fl; Pdx1-Cre (mutant) versus Sox9fl/fl (wild-type) littermates for three biological replicates.

ORGANISM(S): Mus musculus

SUBMITTER: Hung Ping Shih

PROVIDER: E-GEOD-28669 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation.

Shih Hung Ping HP Kopp Janel L JL Sandhu Manbir M Dubois Claire L CL Seymour Philip A PA Grapin-Botton Anne A Sander Maike M

Development (Cambridge, England) 20120606 14

In the pancreas, Notch signaling is thought to prevent cell differentiation, thereby maintaining progenitors in an undifferentiated state. Here, we show that Notch renders progenitors competent to differentiate into ductal and endocrine cells by inducing activators of cell differentiation. Notch signaling promotes the expression of Sox9, which cell-autonomously activates the pro-endocrine gene Ngn3. However, at high Notch activity endocrine differentiation is blocked, as Notch also induces expre ...[more]

PMID: 22675211

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Project description:Memory T cells respond to stimulation with more rapid expression of effector cell functions than their naM-CM-/ve counterparts, yet the gene expression signature underlying this enhanced recall response is not known. Therefore, we performed comprehensive, whole-genome expression profiling of murine memory CD8 T cells before and shortly after ex vivo stimulation. We compared this differential expression profile to its counterpart from stimulated naive cells. Given that memory cells arise from naive cells, the quiescent state of both cell populations prior to stimulation, and the early time point analyzed (four hours post-stimulation), it was possible that the stimulation-induced changes in gene expression were identical between the two populations. While there was a high degree of overlap, we found that the majority of up-regulated genes were more highly induced following stimulation of memory cells. This more robust increase in transcript levels was observed for a functionally diverse set of genes, including cytokines, chemokines, amino acid metabolic enzymes and transporters, transcription factors and regulators of RNA processing. We also identified the unique, stimulation-induced signatures of naive and memory CD8 T cells and found that the former was enriched for factors involved in regulating chromatin modifications. Specifically, we found that Hdac 5,7 and 8 transcript levels were rapidly down-regulated following stimulation of naive cells, which correlated with an increase in their total level of acetylated histone H3 (AcH3). This was in contrast to stimulated memory cells, which had higher levels of total AcH3 ex vivo that did not change following short-term stimulation. Furthermore, the unique stimulation-induced expression profile of memory cells was enriched for factors involved in regulating transport of molecules between the nucleus and cytoplasm, including multiple members of the nuclear pore complex. Together, these results support a model whereby the chromatin modifications that occur during the differentiation of naM-CM-/ve cells into memory cells are preserved in resting memory populations, facilitating their more robust re-activation of a functionally diverse set of genes that contribute to rapid recall of effector functions. NaM-CM-/ve (CD44lo) and memory phenotype (CD44hi) CD8 T cells from 7-wk old female B6 mice were FACS-purified and cultured in vitro for four hours in the presence or absence of PMA and ionomycin. Total RNA was purified from un-stimulated (resting) naM-CM-/ve, resting memory, stimulated naive, and stimulated memory cells and hybridized to individual single-color arrays. This purification and stimulation protocol was performed four independent times.

Dataset Information

Identification of Sox9-Regulated Pathways During Early Pancreas Organogenesis

Publications

A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation.

Similar Datasets

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