The impact of remote solid tumors on bone marrow ecosystem at single-cell resolution

The bone marrow (BM) environment (BME) is inhabited by hematopoietic stem and progenitor cells (HSPCs) and niche cells, which are sources of bone homeostasis, hematopoiesis and immune response. The BM senses many pathological insults, including solid cancers. However, a comprehensive understanding of BM ecosystem response to solid cancer is lacking. Herein, by single-cell RNA sequencing, we characterized the BM landscape in tumor-bearing models prior to metastasis. We found that remote tumors induce dramatic systemic BM niche remodeling that drives HSPC reprogramming and dysfunctional hematopoiesis, which is distinct from innate immune responses. To identify the changes of hematopoietic stem and progenitor cells (HSPCs) and the bone marrow (BM) niche cells in the context of tumor burden, we isolated BM Lin-cKit+ cells (enriched with HSPCs) and CD45-Ter119- cells (niche compartment) from tumor-free (Sham-operated) and mammary tumor (PyMT-N)-bearing mice, then subjected to 3' single-cell RNA sequencing