In summary, our study unveiled a novel role of XIST in promoting ALDH+ CSCs in luminal and TN BC by antagonizing let-7a-2-3p in bulk tumor cells to enhance IL-6 production, which preferentially binds to IL6R on ALDH+ CSCs to drive STAT3 activation and c-MYC, KLF4 and SOX9 expression, promoting self-renewal of ALDH+ CSCs (Fig. 8). Here, IL6 is linked to breast cancer.