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Multiomic Profiling Identifies cis-Regulatory Networks Underlying Human Pancreatic ß Cell Identity and Function.
Lawlor, Nathan; Márquez, Eladio J; Orchard, Peter; Narisu, Narisu; Shamim, Muhammad Saad; Thibodeau, Asa; Varshney, Arushi; Kursawe, Romy; Erdos, Michael R; Kanke, Matt; Gu, Huiya; Pak, Evgenia; Dutra, Amalia; Russell, Sheikh; Li, Xingwang; Piecuch, Emaly; Luo, Oscar; Chines, Peter S; Fuchbserger, Christian; Sethupathy, Praveen; Aiden, Aviva Presser; Ruan, Yijun; Aiden, Erez Lieberman; Collins, Francis S; Ucar, Duygu; Parker, Stephen C J; Stitzel, Michael L.
Afiliação
  • Lawlor N; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
  • Márquez EJ; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
  • Orchard P; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Narisu N; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Shamim MS; Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Computer Science,
  • Thibodeau A; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
  • Varshney A; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Kursawe R; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
  • Erdos MR; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Kanke M; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
  • Gu H; Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
  • Pak E; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Dutra A; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Russell S; Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Computer Science, Department of Computational and Applied Mathematics, Rice University, Houston, TX 77030,
  • Li X; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
  • Piecuch E; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut, Farmington, CT 06032, USA.
  • Luo O; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
  • Chines PS; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Fuchbserger C; Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
  • Sethupathy P; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
  • Aiden AP; Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Bioengineering, Rice University, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medic
  • Ruan Y; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
  • Aiden EL; Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Computer Science, Department of Computational and Applied Mathematics, Rice University, Houston, TX 77030,
  • Collins FS; National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
  • Ucar D; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut, Farmington, CT 06032, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT 06032, USA.
  • Parker SCJ; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  • Stitzel ML; The Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Department of Genetics and Genome Sciences, University of Connecticut, Farmington, CT 06032, USA; Institute for Systems Genomics, University of Connecticut, Farmington, CT 06032, USA. Electronic address: michael.stitzel@jax.org.
Cell Rep ; 26(3): 788-801.e6, 2019 01 15.
Article em En | MEDLINE | ID: mdl-30650367
ABSTRACT
EndoC-ßH1 is emerging as a critical human ß cell model to study the genetic and environmental etiologies of ß cell (dys)function and diabetes. Comprehensive knowledge of its molecular landscape is lacking, yet required, for effective use of this model. Here, we report chromosomal (spectral karyotyping), genetic (genotyping), epigenomic (ChIP-seq and ATAC-seq), chromatin interaction (Hi-C and Pol2 ChIA-PET), and transcriptomic (RNA-seq and miRNA-seq) maps of EndoC-ßH1. Analyses of these maps define known (e.g., PDX1 and ISL1) and putative (e.g., PCSK1 and mir-375) ß cell-specific transcriptional cis-regulatory networks and identify allelic effects on cis-regulatory element use. Importantly, comparison with maps generated in primary human islets and/or ß cells indicates preservation of chromatin looping but also highlights chromosomal aberrations and fetal genomic signatures in EndoC-ßH1. Together, these maps, and a web application we created for their exploration, provide important tools for the design of experiments to probe and manipulate the genetic programs governing ß cell identity and (dys)function in diabetes.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Secretoras de Insulina / Redes Reguladoras de Genes Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Secretoras de Insulina / Redes Reguladoras de Genes Idioma: En Ano de publicação: 2019 Tipo de documento: Article