Single cell sequencing reveals the landscape of the brain metastatic microenvironment
We have applied scRNA-seq and profiled 10,896 cells collected from five brain tumor tissue samples that are metastasis from breast and lung cancer. Our analysis identifies intratumoral components that are predominantly tumor cells, fibroblasts, myeloid cells, stromal cells that express neural stem cell (NSC) markers, with minor populations of oligodendrocytes (oligo) and T cells. Different samples present diverse cell compositions, indicating the underlying cellular interactions that affect different cellular infiltration within TME. Importantly, we identify the tumor-associated fibroblasts that 1) highly expresses type I collagen genes; 2) dominates the cell-cell interactions in TME through the type I collagen signaling axis; and 3) remodels the TME to a collagen-I-rich extracellular matrix (ECM) similar to the original TME at the primary sites. We also observe the M1 activation of the native microglial cells and the infiltrated macrophages, which may create a proinflammatory TME and be responsible for the high expression of collagen type I in fibroblasts. Moreover, the tumor cell-specific receptors are significantly associated with patients’ survival in both brain metastasis and the native glioblastoma cases.
In this Github, we provided the survival analysis codes, which revealed the tumor cell-specific receptors are significantly associated with patients’ survival in glioblastoma cases from TCGA.