Here, by using single-cell RNA sequencing (scRNA-seq) combined with driver mutation detection across ET patients, it is found that MPL-mutated HSCs exhibited aberrant metabolism, CALR-mutated HSCs displayed active cell cycling, while JAK2 <sup>V617F</sup>-mutated HSCs demonstrated enhanced megakaryocyte (Mk) priming capacity and interferon (IFN) response. The gene discussed is CALR; the disease is essential thrombocythemia.