Am J Pathol. 2026 Jan 15:S0002-9440(26)00004-0. doi: 10.1016/j.ajpath.2025.12.010. Online ahead of print.
ABSTRACT
Hematopoietic stem cell (HSC) aging leads to hematological dysfunction and diseases, but the regulatory factors involved remain incompletely characterized. In this study, HasCATs model was developed to identify transcription factors (TFs) that resist HSC aging. This approach revealed RORA as a key Aging-Negative-Associated TF. Rora deletion in HSCs caused aged phenomes and functionally impaired their reconstitutive capacity. Additionally, Rora deficiency impaired leukemia stem cells (LSC) proliferation and prevented Chronic Myelogenous Leukemia (CML). These findings establish RORA as a critical regulator in maintaining HSC function and provide insights into its therapeutic potential in hematological disorders.
PMID:41547479 | DOI:10.1016/j.ajpath.2025.12.010