c-MYC Triggers Lipid Remodelling During Early Somatic Cell Reprogramming to Pluripotency

Fecha de publicación: 01/09/2021 Fecha Ahead of Print: 01/09/2021

Autores de IIS La Fe

Juan Carlos García Cañaveras

Autor
Agustín Lahoz Rodríguez

Autor

Participantes ajenos a IIS La Fe

Prieto, Javier
Leon, Marian
Sendra, Ramon
Ponsoda, Xavier
Izpisua Belmonte, Juan Carlos
Torres, Josema

Grupos

Unidad de Biomarcadores y Medicina de Precisión (UBYMP)

Leader

Agustín Lahoz Rodríguez

Abstract

Metabolic rewiring and mitochondrial dynamics remodelling are hallmarks of cell reprogramming, but the roles of the reprogramming factors in these changes are not fully understood. Here we show that c-MYC induces biosynthesis of fatty acids and increases the rate of pentose phosphate pathway. Time-course profiling of fatty acids and complex lipids during cell reprogramming using lipidomics revealed a profound remodelling of the lipid content, as well as the saturation and length of their acyl chains, in a c-MYC-dependent manner. Pluripotent cells displayed abundant cardiolipins and scarce phosphatidylcholines, with a prevalence of monounsaturated acyl chains. Cells undergoing cell reprogramming showed an increase in mitochondrial membrane potential that paralleled that of mitochondrial-specific cardiolipins. We conclude that c-MYC controls the rewiring of somatic cell metabolism early in cell reprogramming by orchestrating cell proliferation, synthesis of macromolecular components and lipid remodelling, all necessary processes for a successful phenotypic transition to pluripotency.

Datos de la publicación

ISSN/ISSNe:: 2629-3269, 2629-3277
Tipo:: Article
Páginas:: 2245-2261
DOI:: 10.1007/s12015-021-10239-2
Factor de Impacto:: 1,078 SCImago ℠
Cuartil:: Q2 SCImago ℠

Documentos

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Métricas

Filiaciones

Prieto, Javier:: 1 Departamento Biología Celular, Biología Funcional y Antropología Física, Universitat de València, 46100, Burjassot, Valencia, Spain.

2 Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Carlos Garcia-Canaveras, Juan:: Instituto de Investigación. 3 Biomarkers and Precision Medicine Unit, Instituto de Investigación Sanitaria La Fe, 46026, Valencia, Spain.
Leon, Marian:: 1 Departamento Biología Celular, Biología Funcional y Antropología Física, Universitat de València, 46100, Burjassot, Valencia, Spain.
Sendra, Ramon:: 4 Departamento de Bioquímica y Biología Molecular, Universitat de València, 46100, Burjassot, Valencia, Spain.
Ponsoda, Xavier:: 1 Departamento Biología Celular, Biología Funcional y Antropología Física, Universitat de València, 46100, Burjassot, Valencia, Spain.
Izpisua Belmonte, Juan Carlos:: 2 Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, 92037, USA.
Lahoz, Agustin:: Instituto de Investigación. 5 Biomarkers and Precision Medicine Unit, Instituto de Investigación Sanitaria La Fe, 46026, Valencia, Spain.
Torres, Josema:: 6 Departamento Biología Celular, Biología Funcional y Antropología Física, Universitat de València, 46100, Burjassot, Valencia, Spain.

7 Instituto de Investigación Sanitaria (INCLIVA), 46010, Valencia, Spain.

Keywords

COA-CARBOXYLASE-ALPHA; ATP CITRATE LYASE; ACETYL-COA; STEM-CELLS; SUPRAMOLECULAR ORGANIZATION; ENERGY-METABOLISM; CANCER; CARDIOLIPIN; GLYCOLYSIS; SYNTHASE