Updated project metadata. The meninges of the brain are an important component of neuroinflammatory response. Diverse immune cells move from the calvaria marrow into the dura mater via recently discovered skull-meninges connections (SMCs). However, how the calvaria bone marrow is different from the other bones and whether and how it contributes to human diseases remain unknown. Using multi-omics approaches and whole mouse transparency we reveal that bone marrow cells are highly heterogeneous across the mouse body. The mouse calvaria and the human skull harbors the most distinct molecular signature with hundreds of differentially expressed genes and proteins when compared to other bones. Our study indicates that the calvaria is more than a physical barrier, and its immune cells may present new ways to control brain pathologies.