Bone marrow-derived mesenchymal stem cells (BMSCs) aid bone production and serve as the stromal niche for hematopoietic stem cell regulation (HSCs). HSC engraftment upon transplantation is hampered by stromal niche dysfunction, although the underlying processes were unknown. All-trans retinoic acid (ATRA) and inflammatory stress enhanced retinoic acid-inducible gene I (RIG-I) in BMSCs, according to the findings of this study. Furthermore, RIG-I overexpression harmed BMSC clonogenicity, bone-forming capacity, and especially their stromal niche function, favoring HSC proliferation in vitro and engraftment in vivo. 

RIG-I elevation, through changing the RIG-I-Trim25-Keap1-NRF2 complex, enhanced the degradation of NRF2, a checkpoint for an antioxidant cellular response, resulting in ROS buildup and BMSC damage. In ATRA-treated BMSCs, genetic suppression of RIG-I preserved NRF2 protein levels while lowering ROS levels, retaining their clonogenicity, bone-forming capacity, and stromal niche role in promoting HSC engraftment in mice. RIG-I inhibition improved HSC engraftment and emergency myelopoiesis for innate immunity against Listeria monocytogenes the following transplantation by restoring the ATRA-treated stromal niche function. According to the findings, RIG-I has a noncanonical role in the control of the stromal niche for HSC transplantation.