Single-cell transcriptome deciphers key targets of thrombopoietin receptor agonists and immune microenvironment characteristics of immune thrombocytopenia - PubMed
4 hours ago
- #single-cell transcriptomics
- #thrombopoietin receptor agonists
- #immune thrombocytopenia
- Systematic integration of network pharmacology and single-cell RNA-seq analysis identified five key genes (CACNA1A, CSF1R, PKN1, CD9, DSTYK) as targets for TPO-RAs in ITP.
- Molecular docking confirmed strong binding affinities between four TPO-RAs (romiplostim, eltrombopag, avatrombopag, hetrombopag) and these key genes, linking therapeutic effects to thrombopoiesis and immune regulation.
- The bone marrow immune microenvironment in ITP shows rewired cell-cell communication, particularly enhanced T cell signaling and aberrant megakaryocyte-T cell interactions.
- Pseudotime trajectory analysis revealed disrupted megakaryocyte maturation dynamics, contributing to impaired platelet production in ITP.
- In silico knockdown experiments indicated that CACNA1A, CSF1R, and PKN1 dysregulation exacerbates neutrophil hyperactivity, while CD9 and DSTYK knockdown impairs mitotic regulation.