Mesenchymal stem/stromal cells (MSCs) are multipotent progenitors with the ability to sustain hematopoietic cells. Recent findings have showed that MSCs are functionally heterogeneous, i.e. constituted by different subsets of cells with different functions. The identity of the subset of human MSCs involved in hematopoietic support has been so far unknown. In the present study, Corselli et al. identified for the first time CD146+ perivascular cells as the subset of MSCs able to maintain hematopoietic stem and progenitor cells (HSPCs) after ex vivo culture. The authors first demonstrate that CD146+ perivascular cells surround the blood vessels present in human bone marrow and fat. They also show that these cells express markers of the perivascular hematopoietic niche (nestin, CXCL12, leptin receptor), as previously reported in mouse bone marrow. CD146+ cells purified to homogeneity via FACS sorting promoted superior HSPC survival and prevented differentiation toward myeloid or lymphoid lineages as compared to unfractionated and heterogeneous MSCs. Furthermore, only CD146+ could maintain HSPCs with the ability to repopulate the hematopoietic system of immunodeficient mice. Interestingly, CD146+ cells able to support HSPCs were also found in human adipose tissue, an abundant and convenient source of stem cells.