Dose-resolved control of somatic reprogramming by Rora
colony formation, whereas higher expression reduces colonies. Domain dissection separated these arms-DNA-binding domain (DBD)/ligand-binding domain (LBD) was required for the pro-reprogramming effect, while the N-terminal domain (NTD) was required for high-dose inhibition (ΔNTD eliminated the inhibitory limb). Functionally, the reprogramming barrier interferon (IFN)-γ was attenuated at transcript and protein levels; IFN-γ add-back dampened the enhancement, supporting immune-axis modulation. Conversely, WNT pathway output was reduced in the inhibitory arm, and CHIR99021 partially rescued the high-dose colony defect. Thus, RORA acts as a dose-programmed, domain-modular regulator that coordinates chromatin and signaling to gate cell-fate conversion, establishing nuclear-receptor dosage control as a lever to improve reprogramming efficiency.
Authors
- Chang Li (ORCID: https://orcid.org/0000-0002-3267-1859)
- Yi Wang (ORCID: https://orcid.org/0000-0002-8726-402X)
- Lizhan Xiao (ORCID: https://orcid.org/0009-0005-9251-7801)
- Yusha Li (ORCID: https://orcid.org/0000-0003-0484-684X)
- Runxia Lin
- Rongping Luo (ORCID: https://orcid.org/0000-0002-1608-1031)
- Zheng Zhang (ORCID: https://orcid.org/0000-0003-1470-6998)
- Manish Kumar (ORCID: https://orcid.org/0000-0002-3901-9679)
- Chao Yin (ORCID: https://orcid.org/0000-0003-2896-3741)
- Anchun Xu
- Shumin Li
- Jiani Wan
- Bailing Chen
- Lv Zhang
- Xiaoli Zhang
- Yi Li
- Jing Guo
- Jing Liu
- Haiyun Wang
- Shengyong Yu
Institutions
- Fujian Medical University (CN)
- Shanxi University (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Stem Cell Reports
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1016/j.stemcr.2026.102870
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Innovation and Technology Commission
- Natural Science Foundation of Guangdong Province
- Guangzhou Science and Technology Program key projects
- National Key Research and Development Program of China
- Science and Technology Planning Project of Guangdong Province
- National Key Research and Development Program of China Stem Cell and Translational Research
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences
- Basic and Applied Basic Research Foundation of Guangdong Province