Regulation of Neurod1 contributes to the lineage potential of Neurogenin3+ endocrine precursor cells in the pancreas.

Abstract:

:During pancreatic development, transcription factor cascades gradually commit precursor populations to the different endocrine cell fate pathways. Although mutational analyses have defined the functions of many individual pancreatic transcription factors, the integrative transcription factor networks required to regulate lineage specification, as well as their sites of action, are poorly understood. In this study, we investigated where and how the transcription factors Nkx2.2 and Neurod1 genetically interact to differentially regulate endocrine cell specification. In an Nkx2.2 null background, we conditionally deleted Neurod1 in the Pdx1+ pancreatic progenitor cells, the Neurog3+ endocrine progenitor cells, or the glucagon+ alpha cells. These studies determined that, in the absence of Nkx2.2 activity, removal of Neurod1 from the Pdx1+ or Neurog3+ progenitor populations is sufficient to reestablish the specification of the PP and epsilon cell lineages. Alternatively, in the absence of Nkx2.2, removal of Neurod1 from the Pdx1+ pancreatic progenitor population, but not the Neurog3+ endocrine progenitor cells, restores alpha cell specification. Subsequent in vitro reporter assays demonstrated that Nkx2.2 represses Neurod1 in alpha cells. Based on these findings, we conclude that, although Nkx2.2 and Neurod1 are both necessary to promote beta cell differentiation, Nkx2.2 must repress Neurod1 in a Pdx1+ pancreatic progenitor population to appropriately commit a subset of Neurog3+ endocrine progenitor cells to the alpha cell lineage. These results are consistent with the proposed idea that Neurog3+ endocrine progenitor cells represent a heterogeneous population of unipotent cells, each restricted to a particular endocrine lineage.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Mastracci TL,Anderson KR,Papizan JB,Sussel L

doi

10.1371/journal.pgen.1003278

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

e1003278

issue

2

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-12-01591

journal_volume

9

pub_type

杂志文章
  • Drosophila insulin-like peptide 2 mediates dietary regulation of sleep intensity.

    abstract::Sleep is a nearly universal behavior that is regulated by diverse environmental stimuli and physiological states. A defining feature of sleep is a homeostatic rebound following deprivation, where animals compensate for lost sleep by increasing sleep duration and/or sleep depth. The fruit fly, Drosophila melanogaster, ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008270

    authors: Brown EB,Shah KD,Faville R,Kottler B,Keene AC

    更新日期:2020-03-11 00:00:00

  • A genome-wide association study of pulmonary function measures in the Framingham Heart Study.

    abstract::The ratio of forced expiratory volume in one second to forced vital capacity (FEV(1)/FVC) is a measure used to diagnose airflow obstruction and is highly heritable. We performed a genome-wide association study in 7,691 Framingham Heart Study participants to identify single-nucleotide polymorphisms (SNPs) associated wi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000429

    authors: Wilk JB,Chen TH,Gottlieb DJ,Walter RE,Nagle MW,Brandler BJ,Myers RH,Borecki IB,Silverman EK,Weiss ST,O'Connor GT

    更新日期:2009-03-01 00:00:00

  • Limiting of the innate immune response by SF3A-dependent control of MyD88 alternative mRNA splicing.

    abstract::Controlling infectious disease without inducing unwanted inflammatory disease requires proper regulation of the innate immune response. Thus, innate immunity needs to be activated when needed during an infection, but must be limited to prevent damage. To accomplish this, negative regulators of innate immunity limit th...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003855

    authors: De Arras L,Alper S

    更新日期:2013-10-01 00:00:00

  • Optimal sequencing strategies for identifying disease-associated singletons.

    abstract::With the increasing focus of genetic association on the identification of trait-associated rare variants through sequencing, it is important to identify the most cost-effective sequencing strategies for these studies. Deep sequencing will accurately detect and genotype the most rare variants per individual, but may li...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006811

    authors: Rashkin S,Jun G,Chen S,Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO).,Abecasis GR

    更新日期:2017-06-22 00:00:00

  • Improved statistics for genome-wide interaction analysis.

    abstract::Recently, Wu and colleagues [1] proposed two novel statistics for genome-wide interaction analysis using case/control or case-only data. In computer simulations, their proposed case/control statistic outperformed competing approaches, including the fast-epistasis option in PLINK and logistic regression analysis under ...

    journal_title:PLoS genetics

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pgen.1002625

    authors: Ueki M,Cordell HJ

    更新日期:2012-01-01 00:00:00

  • Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals persistent hypomethylation of interferon genes and compositional changes to CD4+ T-cell populations.

    abstract::Systemic lupus erythematosus (SLE) is an autoimmune disease with known genetic, epigenetic, and environmental risk factors. To assess the role of DNA methylation in SLE, we collected CD4+ T-cells, CD19+ B-cells, and CD14+ monocytes from 49 SLE patients and 58 controls, and performed genome-wide DNA methylation analysi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003678

    authors: Absher DM,Li X,Waite LL,Gibson A,Roberts K,Edberg J,Chatham WW,Kimberly RP

    更新日期:2013-01-01 00:00:00

  • Integrating molecular QTL data into genome-wide genetic association analysis: Probabilistic assessment of enrichment and colocalization.

    abstract::We propose a novel statistical framework for integrating the result from molecular quantitative trait loci (QTL) mapping into genome-wide genetic association analysis of complex traits, with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genetic vari...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006646

    authors: Wen X,Pique-Regi R,Luca F

    更新日期:2017-03-09 00:00:00

  • Abnormal type I collagen post-translational modification and crosslinking in a cyclophilin B KO mouse model of recessive osteogenesis imperfecta.

    abstract::Cyclophilin B (CyPB), encoded by PPIB, is an ER-resident peptidyl-prolyl cis-trans isomerase (PPIase) that functions independently and as a component of the collagen prolyl 3-hydroxylation complex. CyPB is proposed to be the major PPIase catalyzing the rate-limiting step in collagen folding. Mutations in PPIB cause re...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004465

    authors: Cabral WA,Perdivara I,Weis M,Terajima M,Blissett AR,Chang W,Perosky JE,Makareeva EN,Mertz EL,Leikin S,Tomer KB,Kozloff KM,Eyre DR,Yamauchi M,Marini JC

    更新日期:2014-06-26 00:00:00

  • A genome-wide screen for bacterial envelope biogenesis mutants identifies a novel factor involved in cell wall precursor metabolism.

    abstract::The cell envelope of Gram-negative bacteria is a formidable barrier that is difficult for antimicrobial drugs to penetrate. Thus, the list of treatments effective against these organisms is small and with the rise of new resistance mechanisms is shrinking rapidly. New therapies to treat Gram-negative bacterial infecti...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004056

    authors: Paradis-Bleau C,Kritikos G,Orlova K,Typas A,Bernhardt TG

    更新日期:2014-01-01 00:00:00

  • The CUGBP2 splicing factor regulates an ensemble of branchpoints from perimeter binding sites with implications for autoregulation.

    abstract::Alternative pre-mRNA splicing adjusts the transcriptional output of the genome by generating related mRNAs from a single primary transcript, thereby expanding protein diversity. A fundamental unanswered question is how splicing factors achieve specificity in the selection of target substrates despite the recognition o...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000595

    authors: Dembowski JA,Grabowski PJ

    更新日期:2009-08-01 00:00:00

  • Multiple mechanisms regulate H3 acetylation of enhancers in response to thyroid hormone.

    abstract::Hormone-dependent activation of enhancers includes histone hyperacetylation and mediator recruitment. Histone hyperacetylation is mostly explained by a bimodal switch model, where histone deacetylases (HDACs) disassociate from chromatin, and histone acetyl transferases (HATs) are recruited. This model builds on decade...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008770

    authors: Præstholm SM,Siersbæk MS,Nielsen R,Zhu X,Hollenberg AN,Cheng SY,Grøntved L

    更新日期:2020-05-26 00:00:00

  • Multifaceted genome control by Set1 Dependent and Independent of H3K4 methylation and the Set1C/COMPASS complex.

    abstract::Histone modifiers are critical regulators of chromatin-based processes in eukaryotes. The histone methyltransferase Set1, a component of the Set1C/COMPASS complex, catalyzes the methylation at lysine 4 of histone H3 (H3K4me), a hallmark of euchromatin. Here, we show that the fission yeast Schizosaccharomyces pombe Set...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004740

    authors: Mikheyeva IV,Grady PJ,Tamburini FB,Lorenz DR,Cam HP

    更新日期:2014-10-30 00:00:00

  • The genetic architecture of the genome-wide transcriptional response to ER stress in the mouse.

    abstract::Endoplasmic reticulum (ER) stress occurs when misfolded proteins accumulate in the ER. The cellular response to ER stress involves complex transcriptional and translational changes, important to the survival of the cell. ER stress is a primary cause and a modifier of many human diseases. A first step to understanding ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004924

    authors: Chow CY,Wang X,Riccardi D,Wolfner MF,Clark AG

    更新日期:2015-02-04 00:00:00

  • Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.

    abstract::A form of dwarfism known as Meier-Gorlin syndrome (MGS) is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5). These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional rep...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007041

    authors: Sanchez JC,Kwan EX,Pohl TJ,Amemiya HM,Raghuraman MK,Brewer BJ

    更新日期:2017-10-16 00:00:00

  • Translesion synthesis polymerases are dispensable for C. elegans reproduction but suppress genome scarring by polymerase theta-mediated end joining.

    abstract::Bases within DNA are frequently damaged, producing obstacles to efficient and accurate DNA replication by replicative polymerases. Translesion synthesis (TLS) polymerases, via their ability to catalyze nucleotide additions to growing DNA chains across DNA lesions, promote replication of damaged DNA, thus preventing ch...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008759

    authors: van Bostelen I,van Schendel R,Romeijn R,Tijsterman M

    更新日期:2020-04-24 00:00:00

  • Fpr1, a primary target of rapamycin, functions as a transcription factor for ribosomal protein genes cooperatively with Hmo1 in Saccharomyces cerevisiae.

    abstract::Fpr1 (FK506-sensitive proline rotamase 1), a protein of the FKBP12 (FK506-binding protein 12 kDa) family in Saccharomyces cerevisiae, is a primary target for the immunosuppressive agents FK506 and rapamycin. Fpr1 inhibits calcineurin and TORC1 (target of rapamycin complex 1) when bound to FK506 and rapamycin, respecti...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008865

    authors: Kasahara K,Nakayama R,Shiwa Y,Kanesaki Y,Ishige T,Yoshikawa H,Kokubo T

    更新日期:2020-06-30 00:00:00

  • The protein quality control machinery regulates its misassembled proteasome subunits.

    abstract::Cellular toxicity introduced by protein misfolding threatens cell fitness and viability. Failure to eliminate these polypeptides is associated with various aggregation diseases. In eukaryotes, the ubiquitin proteasome system (UPS) plays a vital role in protein quality control (PQC), by selectively targeting misfolded ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005178

    authors: Peters LZ,Karmon O,David-Kadoch G,Hazan R,Yu T,Glickman MH,Ben-Aroya S

    更新日期:2015-04-28 00:00:00

  • Allele frequency matching between SNPs reveals an excess of linkage disequilibrium in genic regions of the human genome.

    abstract::Significant interest has emerged in mapping genetic susceptibility for complex traits through whole-genome association studies. These studies rely on the extent of association, i.e., linkage disequilibrium (LD), between single nucleotide polymorphisms (SNPs) across the human genome. LD describes the nonrandom associat...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0020142

    authors: Eberle MA,Rieder MJ,Kruglyak L,Nickerson DA

    更新日期:2006-09-08 00:00:00

  • Negative feedback and transcriptional overshooting in a regulatory network for horizontal gene transfer.

    abstract::Horizontal gene transfer (HGT) is a major force driving bacterial evolution. Because of their ability to cross inter-species barriers, bacterial plasmids are essential agents for HGT. This ability, however, poses specific requisites on plasmid physiology, in particular the need to overcome a multilevel selection proce...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004171

    authors: Fernandez-Lopez R,Del Campo I,Revilla C,Cuevas A,de la Cruz F

    更新日期:2014-02-27 00:00:00

  • Functional male accessory glands and fertility in Drosophila require novel ecdysone receptor.

    abstract::In many insects, the accessory gland, a secretory tissue of the male reproductive system, is essential for male fertility. Male accessory gland is the major source of proteinaceous secretions, collectively called as seminal proteins (or accessory gland proteins), which upon transfer, manipulate the physiology and beha...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1006788

    authors: Sharma V,Pandey AK,Kumar A,Misra S,Gupta HPK,Gupta S,Singh A,Buehner NA,Ravi Ram K

    更新日期:2017-05-11 00:00:00

  • A mutation in the mouse ttc26 gene leads to impaired hedgehog signaling.

    abstract::The phenotype of the spontaneous mutant mouse hop-sterile (hop) is characterized by a hopping gait, polydactyly, hydrocephalus, and male sterility. Previous analyses of the hop mouse revealed a deficiency of inner dynein arms in motile cilia and a lack of sperm flagella, potentially accounting for the hydrocephalus an...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004689

    authors: Swiderski RE,Nakano Y,Mullins RF,Seo S,Bánfi B

    更新日期:2014-10-23 00:00:00

  • Breast cancer DNA methylation profiles are associated with tumor size and alcohol and folate intake.

    abstract::Although tumor size and lymph node involvement are the current cornerstones of breast cancer prognosis, they have not been extensively explored in relation to tumor methylation attributes in conjunction with other tumor and patient dietary and hormonal characteristics. Using primary breast tumors from 162 (AJCC stage ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1001043

    authors: Christensen BC,Kelsey KT,Zheng S,Houseman EA,Marsit CJ,Wrensch MR,Wiemels JL,Nelson HH,Karagas MR,Kushi LH,Kwan ML,Wiencke JK

    更新日期:2010-07-29 00:00:00

  • Drosha promotes splicing of a pre-microRNA-like alternative exon.

    abstract::The ribonuclease III enzyme Drosha has a central role in the biogenesis of microRNA (miRNA) by binding and cleaving hairpin structures in primary RNA transcripts into precursor miRNAs (pre-miRNAs). Many miRNA genes are located within protein-coding host genes and cleaved by Drosha in a manner that is coincident with s...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004312

    authors: Havens MA,Reich AA,Hastings ML

    更新日期:2014-05-01 00:00:00

  • Correction: Pleiotropic Mechanisms Indicated for Sex Differences in Autism.

    abstract::[This corrects the article DOI: 10.1371/journal.pgen.1006425.]. ...

    journal_title:PLoS genetics

    pub_type: 杂志文章,已发布勘误

    doi:10.1371/journal.pgen.1006831

    authors: Mitra I,Tsang K,Ladd-Acosta C,Croen LA,Aldinger KA,Hendren RL,Traglia M,Lavillaureix A,Zaitlen N,Oldham MC,Levitt P,Nelson S,Amaral DG,Hertz-Picciotto I,Fallin MD,Weiss LA

    更新日期:2017-06-07 00:00:00

  • A Parent-of-Origin Effect Impacts the Phenotype in Low Penetrance Retinoblastoma Families Segregating the c.1981C>T/p.Arg661Trp Mutation of RB1.

    abstract::Retinoblastoma (Rb), the most common pediatric intraocular neoplasm, results from inactivation of both alleles of the RB1 tumor suppressor gene. The second allele is most commonly lost, as demonstrated by loss of heterozygosity studies. RB1 germline carriers usually develop bilateral tumors, but some Rb families displ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005888

    authors: Eloy P,Dehainault C,Sefta M,Aerts I,Doz F,Cassoux N,Lumbroso le Rouic L,Stoppa-Lyonnet D,Radvanyi F,Millot GA,Gauthier-Villars M,Houdayer C

    更新日期:2016-02-29 00:00:00

  • Functional assessment of disease-associated regulatory variants in vivo using a versatile dual colour transgenesis strategy in zebrafish.

    abstract::Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005193

    authors: Bhatia S,Gordon CT,Foster RG,Melin L,Abadie V,Baujat G,Vazquez MP,Amiel J,Lyonnet S,van Heyningen V,Kleinjan DA

    更新日期:2015-06-01 00:00:00

  • Threshold-dependent repression of SPL gene expression by miR156/miR157 controls vegetative phase change in Arabidopsis thaliana.

    abstract::Vegetative phase change is regulated by a decrease in the abundance of the miRNAs, miR156 and miR157, and the resulting increase in the expression of their targets, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors. To determine how miR156/miR157 specify the quantitative and qualitative changes in lea...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007337

    authors: He J,Xu M,Willmann MR,McCormick K,Hu T,Yang L,Starker CG,Voytas DF,Meyers BC,Poethig RS

    更新日期:2018-04-19 00:00:00

  • Correction: U87MG Decoded: The Genomic Sequence of a Cytogenetically Aberrant Human Cancer Cell Line.

    abstract::[This corrects the article DOI: 10.1371/journal.pgen.1000832.]. ...

    journal_title:PLoS genetics

    pub_type: 杂志文章,已发布勘误

    doi:10.1371/journal.pgen.1007392

    authors: Clark MJ,Homer N,O'Connor BD,Chen Z,Eskin A,Lee H,Merriman B,Nelson SF

    更新日期:2018-05-16 00:00:00

  • Long-lasting masculinizing effects of postnatal androgens on myelin governed by the brain androgen receptor.

    abstract::The oligodendrocyte density is greater and myelin sheaths are thicker in the adult male mouse brain when compared with females. Here, we show that these sex differences emerge during the first 10 postnatal days, precisely at a stage when a late wave of oligodendrocyte progenitor cells arises and starts differentiating...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007049

    authors: Abi Ghanem C,Degerny C,Hussain R,Liere P,Pianos A,Tourpin S,Habert R,Macklin WB,Schumacher M,Ghoumari AM

    更新日期:2017-11-06 00:00:00

  • Correction: Integrating transcriptomic network reconstruction and eQTL analyses reveals mechanistic connections between genomic architecture and Brassica rapa development.

    abstract::[This corrects the article DOI: 10.1371/journal.pgen.1008367.]. ...

    journal_title:PLoS genetics

    pub_type: 已发布勘误

    doi:10.1371/journal.pgen.1009131

    authors: Baker RL,Leong WF,Brock MT,Rubin MJ,Markelz RJC,Welch S,Maloof JN,Weinig C

    更新日期:2020-10-08 00:00:00