Single-cell transcriptomics profiling the compatibility mechanism of As2O3-indigo naturalis formula based on bone marrow stroma cells - 03/06/22
, Jia Yu b, ⁎ , Yue Gao a, ⁎ Abstract |
Compound realgar natural indigo tablet is the only oral arsenic agent widely used in acute promyelocytic leukemia (APL) treatment. However, as a therapeutic drug for diseases of the blood system, the scientific knowledge of As 2 O 3 -indigo naturalis formula compatibility has not been studied in bone marrow stromal cells (BMSCs). We chose arsenic trioxide (As 2 O 3 : A), tanshinone IIA (T) and indirubin (I) as representative active compounds of realgar, indigo naturalis, and Salvia miltiorrhiza , respectively, to evaluated the pharmaceutical mechanism and the compatibility of ATI (drug combination) using single-cell RNA sequencing (scRNA-seq). The overlapped genes associated with both disease and drug were selected in BMSCs for in-depth analysis. Results show that joint applications of ATI had the strongest therapeutic efficacy in a murine APL model. Lepr-MSCs, OLCs and BMECs were the sensitive cell groups targeted by ATI in the murine APL model. ATI could regulate the related genes of osteogenic differentiation, adipogenic differentiation, and endothelial cell migration in bone marrow mesenchymal lineage cells in murine APL model and improve normal hematopoiesis-related gene expression and poor prognosis of Lepr-MSCs, OLCs and BMECs in mice with leukemia according to scRNA-seq data. The strongest regulatory effects were found in the joint applications of ATI. ATI combination had the potential mechanism to maintain the stability of the hematopoietic microenvironment and promote hematopoiesis to assist in the treatment of APL. This study illustrated the potential mechanism of ATI in regulating BMSCs from the overall perspective of the hematopoietic microenvironment, and broadened the scientific understanding of ATI compatibility in BMSCs.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Lepr-MSCs, OLCs and BMECs were the sensitive cell groups targeted by ATI on BMSCs in the murine APL model. |
• | ATI could regulate the related genes of osteogenic differentiation, adipogenic differentiation, endothelial cell migration and improve poor prognosis in BMSCs in the murine APL model. |
• | Joint applications of ATI had the strongest therapeutic efficacies and had a potential mechanism to promote hematopoiesis to assist in the treatment of APL in the murine APL model. |
Keywords : Bone marrow stroma cells, Acute promyelocytic leukemia (APL), Single-cell RNA sequencing (scRNA-seq), Compatibility, As 2 O 3 -indigo naturalis formula
Abbreviations : APL, scRNA-seq, BMSCs, A, T, I, TCM, ATI
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Vol 151
Article 113182- juillet 2022 Retour au numéro
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