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Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits using LipocyteProfiler.
Laber, Samantha; Strobel, Sophie; Mercader, Josep M; Dashti, Hesam; Dos Santos, Felipe R C; Kubitz, Phil; Jackson, Maya; Ainbinder, Alina; Honecker, Julius; Agrawal, Saaket; Garborcauskas, Garrett; Stirling, David R; Leong, Aaron; Figueroa, Katherine; Sinnott-Armstrong, Nasa; Kost-Alimova, Maria; Deodato, Giacomo; Harney, Alycen; Way, Gregory P; Saadat, Alham; Harken, Sierra; Reibe-Pal, Saskia; Ebert, Hannah; Zhang, Yixin; Calabuig-Navarro, Virtu; McGonagle, Elizabeth; Stefek, Adam; Dupuis, Josée; Cimini, Beth A; Hauner, Hans; Udler, Miriam S; Carpenter, Anne E; Florez, Jose C; Lindgren, Cecilia; Jacobs, Suzanne B R; Claussnitzer, Melina.
Afiliación
  • Laber S; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Strobel S; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, UK.
  • Mercader JM; Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Dashti H; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Dos Santos FRC; Institute of Nutritional Medicine, School of Medicine, Technical University of Munich, 85354 Freising-Weihenstephan, Germany.
  • Kubitz P; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Jackson M; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Ainbinder A; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
  • Honecker J; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Agrawal S; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
  • Garborcauskas G; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Stirling DR; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Leong A; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Figueroa K; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Sinnott-Armstrong N; Else Kröner-Fresenius-Centre for Nutritional Medicine, School of Life Sciences, Technical University of Munich, 85354 Freising-Weihenstephan, Germany.
  • Kost-Alimova M; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Deodato G; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Harney A; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Way GP; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Saadat A; Else Kröner-Fresenius-Centre for Nutritional Medicine, School of Life Sciences, Technical University of Munich, 85354 Freising-Weihenstephan, Germany.
  • Harken S; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Reibe-Pal S; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ebert H; Imaging Platform, Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Zhang Y; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Calabuig-Navarro V; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • McGonagle E; Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
  • Stefek A; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Dupuis J; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Cimini BA; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Hauner H; Department of Genetics, Stanford University, San Francisco, CA, USA.
  • Udler MS; Imaging Platform, Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Carpenter AE; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Florez JC; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lindgren C; Imaging Platform, Center for the Development of Therapeutics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Jacobs SBR; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Claussnitzer M; Programs in Metabolism and Medical and Population Genetics, Type 2 Diabetes Systems Genomics Initiative, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cell Genom ; 3(7): 100346, 2023 Jul 12.
Article en En | MEDLINE | ID: mdl-37492099
ABSTRACT
A primary obstacle in translating genetic associations with disease into therapeutic strategies is elucidating the cellular programs affected by genetic risk variants and effector genes. Here, we introduce LipocyteProfiler, a cardiometabolic-disease-oriented high-content image-based profiling tool that enables evaluation of thousands of morphological and cellular profiles that can be systematically linked to genes and genetic variants relevant to cardiometabolic disease. We show that LipocyteProfiler allows surveillance of diverse cellular programs by generating rich context- and process-specific cellular profiles across hepatocyte and adipocyte cell-state transitions. We use LipocyteProfiler to identify known and novel cellular mechanisms altered by polygenic risk of metabolic disease, including insulin resistance, fat distribution, and the polygenic contribution to lipodystrophy. LipocyteProfiler paves the way for large-scale forward and reverse deep phenotypic profiling in lipocytes and provides a framework for the unbiased identification of causal relationships between genetic variants and cellular programs relevant to human disease.
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Texto completo: 1 Bases de datos: MEDLINE Idioma: En Revista: Cell Genom Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Idioma: En Revista: Cell Genom Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos