UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Trajectory analysis of hepatic stellate cell differentiation reveals metabolic regulation of cell commitment and fibrosis

Martinez Garcia de la Torre, Raquel A; Vallverdu, Julia; Xu, Zhenqing; Arino, Silvia; Ferrer-Lorente, Raquel; Zanatto, Laura; Mercado-Gomez, Maria; ... Sancho-Bru, Pau; + view all (2025) Trajectory analysis of hepatic stellate cell differentiation reveals metabolic regulation of cell commitment and fibrosis. Nature Communications , 16 (1) , Article 1489. 10.1038/s41467-025-56024-4. Green open access

[thumbnail of Published trajectory Papaer 2025.pdf]
Preview
PDF
Published trajectory Papaer 2025.pdf - Published Version

Download (8MB) | Preview

Abstract

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.

Type: Article
Title: Trajectory analysis of hepatic stellate cell differentiation reveals metabolic regulation of cell commitment and fibrosis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-025-56024-4
Publisher version: https://doi.org/10.1038/s41467-025-56024-4
Language: English
Additional information: © 2025 Springer Nature Limited. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Mental Health Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/10207720
Downloads since deposit
7Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item