Aplastic anemia (AA) is a lethal hematological disorder; however, its pathogenesis is not fully understood. Although immunosuppressive therapy (IST) is a major treatment option for AA, one-third of patients do not respond to IST and its resistance mechanism remains elusive. To understand AA pathogenesis and IST resistance, we performed single-cell RNA sequencing (scRNA-seq) of bone marrow (BM) from healthy controls and patients with AA at diagnosis. We found that CD34(+) early-stage erythroid precursor cells and PROM1(+) hematopoietic stem cells were significantly depleted in AA, which suggests that the depletion of CD34(+) early-stage erythroid precursor cells and PROM1(+) hematopoietic stem cells might be one of the major mechanisms for AA pathogenesis related with BM-cell hypoplasia. More importantly, we observed the significant enrichment of CD8(+) T cells and T cell-activating intercellular interactions in IST responders, indicating the association between the expansion and activation of T cells and the positive response of IST in AA. Taken together, our findings represent a valuable resource offering novel insights into the cellular heterogeneity in the BM of AA and reveal potential biomarkers for IST, building the foundation for future precision therapies in AA.