Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/225236
Trajectory analysis of hepatic stellate cell differentiation reveals metabolic regulation of cell commitment and fibrosis
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Defining the trajectory of cells during differentiation and disease is key for uncovering the mechanisms driving cell fate and identity. However, trajectories of human cells remain largely unexplored due to the challenges of studying them with human samples. In this study, we investigate the proteome trajectory of iPSCs differentiation to hepatic stellate cells (diHSCs) and identify RORA as a key transcription factor governing the metabolic reprogramming of HSCs necessary for diHSCs' commitment, identity, and activation. Using RORA deficient iPSCs and pharmacologic interventions, we show that RORA is required for early differentiation and prevents diHSCs activation by reducing the high energetic state of the cells. While RORA knockout mice have enhanced fibrosis, RORA agonists rescue multi-organ fibrosis in in vivo models. Notably, RORA expression correlates negatively with liver fibrosis and HSCs activation markers in patients with liver disease. This study reveals that RORA regulates cell metabolic plasticity, important for mesoderm differentiation, pericyte quiescence, and fibrosis, influencing cell commitment and disease.
Matèries
Matèries (anglès)
Citació
Citació
MARTÍNEZ GARCÍA DE LA TORRE, Raquel a., VALLVERDÚ GINÈS, Júlia, XU, Zhenqing, ARIÑO, Silvia, FERRER LORENTE, Raquel, ZANATTO, Laura, MERCADO-GÓMEZ, Maria, AGUILAR-BRAVO, Beatriz, RUIZ-BLÁZQUEZ, Paloma, FERNANDEZ-FERNANDEZ, Maria, NAVARRO GASCÓN, Artur, BLASCO ROSET, Albert, SÀNCHEZ FERNÀNDEZ DE LANDA, Paula, PERA, Joan, ROMERO MOYA, Damià, AYUSO GARCIA, Paula, MARTÍNEZ SÁNCHEZ, Celia, SEREROLS VIÑAS, Laura, CANTALLOPS VILÀ, Paula, CÁRCAMO GIRÁLDEZ, Carmen i., MCQUILLIN, Andrew, MORGAN, Marsha y., MOYA RULL, Daniel, MONTSERRAT, Núria, EBERLÉ, Delphine, STAELS, Bart, ANTOINE, Bénédicte, AZKARGORTA, Mikel, LOZANO, Juan-josé, MARTÍNEZ CHANTAR, Maria luz, GIORGETTI, Alessandra, ELORTZA, Felix, PLANAVILA PORTA, Ana, VARELA REY, Marta, WOODHOO, Ashwin, ZORZANO OLARTE, Antonio, GRAUPERA, Isabel, MOLES, Anna, COLL, Mar, AFFÒ, Silvia, SANCHO-BRU, Pau. Trajectory analysis of hepatic stellate cell differentiation reveals metabolic regulation of cell commitment and fibrosis. _Nature Communications_. 2025. Vol. 16, núm. 1. [consulta: 30 de gener de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/225236]