The Regulation of Bone Marrow Mesenchymal Stem Cells by Vascular Cell Adhesion Molecule-1

Bone marrow (BM) mesenchymal stem cells (MSCs) form specialized perivascular microenvironments or niches in the BM that regulate hematopoietic stem cell (HSC) function. Interactions between MSC niche factors and HSCs ensure hematopoietic homeostasis. Vascular Cell Adhesion Molecule-1 (VCAM1) is classically expressed on endothelial and stromal cells. While the contribution of endothelial-derived VCAM1 to BM homeostasis has been extensively studied, the specific role of MSC-derived VCAM1 remains unclear. Here we show that deletion of Vcam1 significantly impacts BM MSC survival by mediating PI3k/Akt signaling. Furthermore, Vcam1-null MSCs display enhanced osteolineage capacity. Surprisingly, VCAM1 loss and associated MSC death did not affect BM HSCs. Single-cell RNA-sequencing of pooled BM and compact bone sorted stromal cells revealed that vascular and perivascular cell populations compensate for a defective MSC niche. These studies demonstrate that MSC-derived Vcam1 is critical for BM MSC survival, osteolineage output, and maintenance of niche integrity.