105 research outputs found

    TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors.

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    The genomic regulatory programmes that underlie human organogenesis are poorly understood. Pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer and diabetes. We have now characterized the regulatory landscape of embryonic multipotent progenitor cells that give rise to all pancreatic epithelial lineages. Using human embryonic pancreas and embryonic-stem-cell-derived progenitors we identify stage-specific transcripts and associated enhancers, many of which are co-occupied by transcription factors that are essential for pancreas development. We further show that TEAD1, a Hippo signalling effector, is an integral component of the transcription factor combinatorial code of pancreatic progenitor enhancers. TEAD and its coactivator YAP activate key pancreatic signalling mediators and transcription factors, and regulate the expansion of pancreatic progenitors. This work therefore uncovers a central role for TEAD and YAP as signal-responsive regulators of multipotent pancreatic progenitors, and provides a resource for the study of embryonic development of the human pancreas

    Clusters of Conserved Beta Cell Marker Genes for Assessment of Beta Cell Phenotype

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    The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

    Expanded encyclopaedias of DNA elements in the human and mouse genomes

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    All data are available on the ENCODE data portal: www.encodeproject. org. All code is available on GitHub from the links provided in the methods section. Code related to the Registry of cCREs can be found at https:// github.com/weng-lab/ENCODE-cCREs. Code related to SCREEN can be found at https://github.com/weng-lab/SCREEN.© The Author(s) 2020. The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.This work was supported by grants from the NIH under U01HG007019, U01HG007033, U01HG007036, U01HG007037, U41HG006992, U41HG006993, U41HG006994, U41HG006995, U41HG006996, U41HG006997, U41HG006998, U41HG006999, U41HG007000, U41HG007001, U41HG007002, U41HG007003, U54HG006991, U54HG006997, U54HG006998, U54HG007004, U54HG007005, U54HG007010 and UM1HG009442

    Talent Selection and the Funding of Research

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    Contains fulltext : 131402.pdf (author's version ) (Open Access) Contains fulltext : 131402-p.pdf (publisher's version ) (Closed access)In a recent issue of this journal, we analyzed decision making about grant applications. We argued that there are many uncertainties in selecting the best talents, and we showed that in quite some cases (i) peer review scores hardly influence the decisions, and (ii) differences between success and no success are very small. The council we studied contested our conclusions. In this short article, we present additional evidence supporting our claims.7 p

    The selection of talent as a group process. A literature review on the social dynamics of decision making in grant panels

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    Contains fulltext : 141696.pdf (author's version ) (Open Access)Talent selection within science is increasingly performed by panels, e.g. by reviewing grant or fellowship applications. Many studies from fields of sociology of science and science policy studies have been conducted to identify biases and predict outcomes of these processes, mainly focusing on characteristics of applicants, applications, and reviewers. However, as panel reviewing entails social interaction, group dynamics influence these processes. By adding insights from social psychology to current knowledge on panel reviews, we are better able to identify factors affecting talent selection and funding decisions in grant panels. By opening up this so-called black box, we aim to contribute to a better understanding of the dynamics of panel decision making. This knowledge is also relevant for various stakeholders involved in grant allocation, for applicants, reviewers, and policymakers, as it can be used to improve transparency, fairness, and legitimation of talent selection processes.18 augustus 201414 p

    Talent centraal. Ontwikkeling en selectie van wetenschappens in Nederland

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    Contains fulltext : 131517.pdf (publisher's version ) (Open Access)Universiteiten richten zich steeds nadrukkelijker op het aantrekken en behouden van wetenschappelijk talent. Het begrip talent heeft hierdoor een centrale plaats verworven in het universitaire personeelsbeleid. Wie zijn nu deze talenten en hoe is talentselectie georganiseerd? De explosief gegroeide aandacht voor talentbeleid, de beperkte academische loopbaanmogelijkheden voor jonge onderzoekers en de hoge aanvraagdruk voor talentgerichte beurzen, vragen om een nadere analyse van de huidige koers van talentselectie in Nederland. In dit rapport laat het Rathenau Instituut zien hoe het huidige systeem van talentselectie in de Nederlandse academische organisatie uitwerkt voor de drie centrale partijen: de universiteit als werkgever, de (jonge) onderzoeker als werknemer en NWO als leverancier van persoonsgerichte beurzen. We signaleren diverse fricties in het huidige systeem die vragen om verdere discussie en oplossingen. Op het einde van het rapport schetsen we enkele scenario’s waarin we alternatieven verkennen die deze spanningen zouden kunnen verlichten.94 p
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