The global gene expression profile of the secondary transition during pancreatic development. (February 2016)

• Record Type: Journal Article
• Authors: Willmann, Stefanie J.; Mueller, Nikola S.; Engert, Silvia; Sterr, Michael; Burtscher, Ingo; Raducanu, Aurelia; Irmler, Martin; Beckers, Johannes; Sass, Steffen; Theis, Fabian J.; Lickert, Heiko
• Is Part Of: Mechanisms of development. Volume 139(2016)
• Page Start: 51
• Page End: 64
• Publication Date: 2016-02
• Subjects: 2210010C04Rik RIKEN cDNA 2210010C04 gene -- 5330417C22Rik RIKEN cDNA 5330417C22 gene -- A1AT alpha1-antitrypsin -- Ago1 argonaute RISC catalytic component 1 -- Amy2a5 amylase 2a5 -- Amy2b amylase, alpha 2B -- AP1/JUN jun proto-oncogene -- Bmp bone morphogenetic protein -- CAM cell adhesion molecule -- CD49f Integrin subunit alpha 6 (Itga6) -- Cela1 chymotrypsin-like elastase family member 1 -- ChIP-seq chromatin-immunoprecipitation sequencing -- Cldn10 Claudin 10 -- Cpa1 carboxypeptidase 1 -- Drosha drosha, ribonuclease type III -- E embryonic day -- ECM extracellular matrix -- Edaradd ectodysplasin-A receptor (EDAR)-associated adapter protein -- EGF epidermal growth factor -- EMT epithelial–mesenchymal transition -- En1 engrailed homeobox 1 -- FACS fluorescence activated cell sorting -- FGF fibroblast growth factor -- Fgf1 fibroblast growth factor 1 -- Fgf10 fibroblast growth factor 10 -- Fgf15 fibroblast growth factor 15 -- Fgf20 fibroblast growth factor 20 -- Fgf23 fibroblast growth factor 23 -- Fgf6 fibroblast growth factor 6 -- Fgf7 fibroblast growth factor 7 -- Fgf8 fibroblast growth factor 8 -- Fgf9 fibroblast growth factor 9 -- Foxa2 Forkhead-Box-Protein A2 -- FVF− Foxa2-Venus negative -- FVF+ Foxa2-Venus positive -- Fzd9 frizzled homolog 9 -- Fzd10 frizzled homolog 10 -- G6pc2 glucose-6-phosphatase, catalytic, 2 -- Gata6 GATA binding protein 6 -- Gck glucokinase -- Gdf10 growth differentiation factor 10 -- Ghr growth hormone receptor -- Ghrl ghrelin/obestatin prepropeptide -- Gip gastric inhibitory polypeptide -- Gipr gastric inhibitory polypeptide receptor -- Gli3 GLI-Kruppel family member GLI3 -- Glp1 glucagon-like peptide 1 -- Glp1r glucagon-like peptide 1 receptor -- GO gene ontology -- Grb7 growth factor receptor bound protein 7 -- GRNs gene regulation networks -- GWAS genome-wide association study -- H3K27ac histone 3 lysine 27 acetylation -- H3K4me1 histone 3 lysine 4 monomethylation -- H3K4me3 histone 3 lysine 4 trimethylation -- Hdac1 histone deacetylase 1 -- Hes1 hairy and enhancer of split 1 -- Hey1 hairy/enhancer-of-split related with YRPW motif 1 -- Hh Hedgehog -- Hhex hematopoietically expressed homeobox -- High mag higher magnitude -- HNF hepatocyte nuclear factor -- Hnf1a hepatocyte nuclear factor 1, alpha -- Hnf1b hepatocyte nuclear factor 1, beta -- Hnf4a hepatocyte nuclear factor 4, alpha -- Hnf4b hepatocyte nuclear factor 4, beta -- Iaap islet amyloid polypeptide -- Igf1 insulin-like growth factor 1 -- Igfbp4/5 insulin-like growth factor binding protein 4/5 -- Ihh Indian hedgehog -- Il11ra2 interleukin 11 receptor, alpha chain 2 -- Ins1 insulin 1 -- Ins2 insulin 2 -- Insrr insulin receptor-related receptor -- iPSC induced pluripotent stem cells -- Isl1 ISL LIM homeobox 1 -- Jag1 jagged1 -- Lum Lumican -- MAF v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog -- MAFB v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B -- Med12 mediator complex subunit 12 -- Med23 mediator complex subunit 23 -- Mist1/Bhlha15 basic helix-loop-helix family, member A15 -- MODY maturity-onset diabetes of the young -- MPC multipotent progenitors -- NeuroD1 neurogenic differentiation 1 -- Ngn3 Neurogenin 3 -- Nkx2-2 NK2 homeobox 2 -- Nkx6.1 NK6 homeobox 1 -- Npy neuropeptide Y -- Nr5a2 nuclear receptor subfamily 5 -- Onecut1/Hnf6 one cut homeobox 1 -- Onecut3 one cut domain, family member 3 -- Osr1 odd-skipped related 1 -- Otx2 orthodenticle homeobox 2 -- Pax4 paired box 4 -- Pax6 paired box 6 -- PC principal component -- Pcsk1-3 proprotein convertase subtilisin/kexin type 1–3 -- Pdgfc platelet derived growth factor C -- Pdx1 pancreatic duodenal transcription homeobox 1 factor -- Pgf placental growth factor -- Ptf1a pancreas specific transcription factor, 1a -- Pyy peptide YY -- RA retinoic acid -- Rbm47 RNA binding motif protein 47 -- Rxrg retinoic acid receptor gamma -- Scgn secretagogin, EF-hand calcium binding protein -- Sdf1 stromal cell-derived factor 1 -- Serpina10 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 10 -- Serpina1a serine (or cysteine) preptidase inhibitor, clade A, member 1A -- Serpina1b serine (or cysteine) preptidase inhibitor, clade A, member 1B -- Serpina1d serine (or cysteine) preptidase inhibitor, clade A, member 1D -- Serpina1e serine (or cysteine) preptidase inhibitor, clade A, member 1E -- Sfrp1 secreted frizzled-related protein 1 -- Shh sonic hedgehog -- Six3 sine oculis-related homeobox 3 -- Slc2a2 solute carrier family 2 (facilitated glucose transporter), member 2 -- Slc30a8 solute carrier family 30 (zinc transporter), member 8 -- Slc38a3 solute carrier family 38, member 3 -- Smarca2 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2 -- Smarca4 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 -- Smarcc1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily c, member 1 -- Smarcc2 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily c, member 2 -- Smarcd1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1 -- Smarcd1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 1 -- Smarce1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily e, member 1 -- Snai1/2 snail family zinc finger 1/2 -- Sox11 SRY (sex determining region Y)-box 11 -- Sox9 SRY (sex determining region Y)-box 9 -- Srpx2 sushi-repeat-containing protein, X-linked 2 -- Sst somatostatin -- Syt13 synaptotagmin 13 -- Syt6 synaptotagmin 6 -- Syt7 synaptotagmin 7 -- Syt8 synaptotagmin 8 -- Sytl1 synaptotagmin-like 1 -- Sytl4 synaptotagmin-like 4 -- T1/2D type 1/2 diabetes -- Tbx19 T-box 19 -- Tbx6 T-box 6 -- Tcf7l1 transcription factor 7-like 1 -- Tcf7l2 transcription factor 7-like 2 -- Tenc1 tensin like C1 domain-containing phosphatase -- TF transcription factor -- TFBS transcription factor binding site -- Tgfß transforming growth factor, beta 1 -- Thbs2 thrombospondin 2 -- Tmem171 transmembrane protein 171 -- TSS transcriptional starting site -- Twist1 twist family bHLH transcription factor 1 -- Vdr vitamin D receptor -- Vwa5b2 von Willebrand factor A domain containing 2B2 -- Wnt wingless -- Wnt1 wingless-type MMTV integration site family, member 1 -- Wnt10a wingless-type MMTV integration site family, member 10A -- Wnt10b wingless-type MMTV integration site family, member 10B -- Wnt2 wingless-type MMTV integration site family, member 2 -- Wnt3a wingless-type MMTV integration site family, member 3A -- Wnt4 wingless-type MMTV integration site family, member 4 -- Wnt5a wingless-type MMTV integration site family, member 5A -- Wnt6 wingless-type MMTV integration site family, member 6 -- Zeb1/2 zinc finger E-box binding homeobox 1/2; Pancreas -- Endocrine -- Exocrine -- Ductal -- Organogenesis -- Foxa2; Developmental biology -- Periodicals; Molecular biology -- Periodicals; Developmental Biology -- Periodicals; Molecular Biology -- Periodicals; Biologie du développement -- Périodiques; Biologie moléculaire -- Périodiques; Developmental biology; Molecular biology; Periodicals; Electronic journals; 571.8
• DOI: 10.1016/j.mod.2015.11.004
• Languages: English
• ISSNs: 0925-4773

Abstract

Abstract: Pancreas organogenesis is a highly dynamic process where neighboring tissue interactions lead to dynamic changes in gene regulatory networks that orchestrate endocrine, exocrine, and ductal lineage formation. To understand the spatio-temporal regulatory logic we have used the Forkhead transcription factor Foxa2-Venus fusion (FVF) knock-in reporter mouse to separate the FVF + pancreatic epithelium from the FVF − surrounding tissue (mesenchyme, neurons, blood, and blood vessels) to perform a genome-wide mRNA expression profiling at embryonic days (E) 12.5–15.5. Annotating genes and molecular processes suggest that FVF marks endoderm-derived multipotent epithelial progenitors at several lineage restriction steps, when the bulk of endocrine, exocrine and ductal cells are formed during the secondary transition. In the pancreatic epithelial compartment, we identified most known endocrine and exocrine lineage determining factors and diabetes-associated genes, but also unknown genes with spatio-temporal regulated pancreatic expression. In the non-endoderm-derived compartment, we identified many well-described regulatory genes that are not yet functionally annotated in pancreas development, emphasizing that neighboring tissue interactions are still ill defined. Pancreatic expression of over 635 genes was analyzed with the mRNA in situ hybridization Genepaint public database. This validated the quality of the profiling data set and identified hundreds of genes with spatially restricted expression patterns in the pancreas. Some of these genes are also targeted by pancreatic transcription factors and show active chromatin marks in human islets of Langerhans. Thus, with the highest spatio-temporal resolution of a global gene expression profile during the secondary transition, our study enables to shed light on neighboring tissue interactions, developmental timing and diabetes gene regulation. Highlights: High-resolution spatio-temporal gene expression profile of pancreas development Cell type-specific profile reveals known and many novel developmental regulators. Differential expression in pancreatic compartments reveals details about tissue interactions. In situ mRNA expression analysis validates tissue specificity and spatial expression. The established resource is of unique value to study mouse and human development and diabetes.