ArrayExpress Uploaderarrayexpress_sidmouseE11.5Sox9wild typeE11.5Sox9wild typeE11.5Sox9wild typeE11.5Sox9wild typeE15.5Progenitorwild typeE15.5Progenitorwild typeE15.5Progenitorwild typeE15.5Acinarwild typeE15.5Acinarwild typeE15.5Acinarwild typeE15.5Endocrine Progenitorwild typeE15.5Endocrine Progenitorwild typeE15.5Endocrine Progenitorwild typeE15.5Neurog3-null cellsNgn3-nullE15.5Neurog3-null cellsNgn3-nullE15.5Neurog3-null cellsNeurog3-nullE15.5Neurog3-null cellsNeurog3-nullE15.5beta cellwild typeE15.5beta cellwild typeE15.5beta cellwild typeE15.5beta cellwild typeE17.5beta cellwild typeE17.5beta cellwild typeE17.5beta cellwild typeP0beta cellwild typeP0beta cellwild typeP0beta cellwild typeP15beta cellwild typeP15beta cellwild typeP15beta cellwild typeP15beta cellwild type8-12wkbeta cellwild type8-12wkbeta cellwild type8-12wkbeta cellwild type8-12wkbeta cellwild typeP0alpha cellwild typeP0alpha cellwild typeP0alpha cellwild typeP0alpha cellwild type8-12wkalpha cellwild type8-12wkalpha cellwild type8-12wkalpha cellwild type8-12wkalpha cellwild type8-12wkalpha cellwild type8-12wkDuct Cellwild type8-12wkDuct Cellwild type8-12wkDuct Cellwild type8-12wkDuct Cellwild type755006The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains...E-GEOD-54374/profile/8773/arrayexpressuploader348celldiabetes mellitusendocrine cellglucosepancreasproteinsurfaceDec.12, 2014FalseE-GEOD-54374_A-AFFY-45an-integrated-cell-purification-and-genomics-stratAn integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.Nov.12, 2014The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene modules in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Module network analysis linked established regulators like Neurog3 to unrecognized roles in endocrine secretion and protein transport, and nominated multiple candidate regulators of pancreas development. Phenotyping mutant mice revealed that candidate regulatory genes encoding transcription factors, including Bcl11a, Etv1, Prdm16 and Runx1t1, are essential for pancreas development or glucose control. Our integrated approach provides a unique framework for identifying regulatory networks underlying pancreas development and diseases like diabetes mellitus. Gene expression analysis: 12 primary cell populations from wild-type pancreas and 1 cell type from a mutant background (E15 Ngn3-null cells) pancreas (in fetal and adult stage) were purified using a combination of cell surface markers and transgenic reporters. Total RNA was isolated from each cell type in at least biological triplicates, amplified and hybridized to Affymetrix Mouse 430 2.0 arrays.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-54374http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-54374/samples/