PXD058290

PXD058290 is an original dataset announced via ProteomeXchange.

Title	TRAJECTORY ANALYSIS OF HEPATIC STELLATE CELL DIFFERENTIATION REVEALS METABOLIC REGULATION OF CELL COMMITMENT AND FIBROSIS
Description	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 investigated the proteome trajectory of iPSCs differentiation to hepatic stellate cells (diHSCs) and identified RORA as a key transcription factor governing the metabolic reprogramming of HSCs necessary for HSCs’ commitment, identity, and activation. Using RORA deficient iPSCs and pharmacologic interventions, we showed that RORA is required for early differentiation and prevents diHSCs activation by reducing the high energetic state of the cells. While RORA knockout mice had enhanced fibrosis, whereas RORA agonists rescued multi-organ fibrosis in in vivo models. Notably, RORA expression was consistently found to be negatively correlated with liver fibrosis and HSCs activation markers in patients with liver disease. This study reveals that RORA regulates cell metabolic plasticity, crucial for mesoderm differentiation, pericyte quiescence, and fibrosis, influencing cell commitment and disease.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_05:39:27.539.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mikel Azkargorta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-26 07:49:38	ID requested
⏵ 1	2025-05-07 05:39:28	announced

10.1038/s41467-025-56024-4;

Mart, í, nez Garc, í, a de la Torre RA, Vallverd, ú J, Xu Z, Ari, ñ, o S, Ferrer-Lorente R, Zanatto L, Mercado-G, ó, mez M, Aguilar-Bravo B, Ruiz-Bl, á, zquez P, Fernandez-Fernandez M, Navarro-Gascon A, Blasco-Roset A, S, à, nchez-Fern, à, ndez-de-Landa P, Pera J, Romero-Moya D, Ayuso Garcia P, Mart, í, nez S, á, nchez C, Sererols Vi, ñ, as L, Cantallops Vil, à P, C, á, rcamo Gir, á, ldez CI, McQuillin A, Morgan MY, Moya-Rull D, Montserrat N, Eberl, é D, Staels B, Antoine B, Azkargorta M, Lozano JJ, Mart, í, nez-Chantar ML, Giorgetti A, Elortza F, Planavila A, Varela-Rey M, Woodhoo A, Zorzano A, Graupera I, Moles A, Coll M, Affo S, Sancho-Bru P, Trajectory analysis of hepatic stellate cell differentiation reveals metabolic regulation of cell commitment and fibrosis. Nat Commun, 16(1):1489(2025) [pubmed]

submitter keyword: iPSCs, diHSCs, RORA, metabolic plasticity

Felix Elortza
contact affiliation	Proteomics Platform CIC bioGUNE Bizkaia Tech. Park Build. 800 48160 Derio (Spain)
contact email	felortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD058290

PRIDE project URI

• PRIDE
  1. PXD058290
     1. Label: PRIDE project
     2. Name: TRAJECTORY ANALYSIS OF HEPATIC STELLATE CELL DIFFERENTIATION REVEALS METABOLIC REGULATION OF CELL COMMITMENT AND FIBROSIS