Ruxolitinib improves hematopoietic regeneration by retrieving mesenchymal stromal cell function in aGVHD

Acute graft-versus-host disease (aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation. Hematopoietic dysfunction accompanied by severe aGVHD, which may be caused by niche impairment, is a long-standing clinical problem. However, how the bone marrow (BM) niche is damaged in aGVHD hosts is poorly defined. To comprehensively address this question, we employed a haplo-MHC-matched transplantation aGVHD murine model and performed single-cell RNA sequencing of non-hematopoietic BM cells. Transcriptional analysis showed that BM mesenchymal stromal cells (BMSCs) were severely affected with a reduction in cell ratio, abnormal metabolism, compromised differentiation potential and defective hematopoietic supportive function, which were validated by functional assays. Overall design: By combining scRNA-seq with functional assays, we revealed a novel mechanism underlying the effect of ruxolitinib on aGVHD niche components and broadened the BMSC-based therapy for aGVHD.