Rora Regulates Hematopoietic Stem Cell Phenotypes and Progression of Chronic Myelogenous Leukemia.

Ning Li, Yunyu Feng, Nan Wang, Wei He, Hongjian Li, Xue Cui, Bochuan Wang, Runkuan Qin, Huandi Qiu, Qiang Qiu, Li Zheng, Yuanyuan Sun, Linye He, Cong Pan, Anping Su, Zhihui Li, Yiguo Hu

State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. · pubmed

Paper

Abstract

Hematopoietic stem cell (HSC) aging leads to hematological dysfunction and diseases, but the regulatory factors involved remain incompletely characterized. In this study, the HSC Aging-Associated TFs Catalog System 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 cell proliferation and prevented chronic myelogenous leukemia. These findings establish RORA as a critical regulator in maintaining HSC function and provide insights into its therapeutic potential in hematological disorders.

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Research summary

Rora is identified as a key transcription factor that regulates hematopoietic stem cell aging and function. The study addresses the regulatory factors involved in HSC aging, which is directly related to the mechanisms of aging and potential interventions for age-related hematological disorders.

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