A unique bone marrow niche composed of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) was identified. Nestin-positive MSCs, identified by nestin expression, are essential components of the HSC niche. These cells are spatially associated with HSCs and adrenergic nerve fibers, and highly express genes involved in HSC maintenance. Nestin-positive MSCs can self-renew and expand in serial transplantations, and are capable of differentiating into osteoblasts, adipocytes, and chondrocytes. They are also required for HSC maintenance and homing in the bone marrow. Nestin-positive MSCs are distinct from osteoblasts and pre-osteoblasts, and are quiescent but metabolically active. They are regulated by the sympathetic nervous system and parathyroid hormone, and their function is essential for maintaining the HSC niche. The study reveals a novel partnership between two distinct somatic stem-cell types, indicating a unique niche in the bone marrow composed of heterotypic stem-cell pairs. The findings suggest that nestin-positive MSCs are bona fide MSCs capable of self-renewal in serial transplantations and contribute to the physiological formation of osteochondral lineages. The study also highlights the importance of nestin-positive MSCs in regulating HSC maintenance and progenitor homing.A unique bone marrow niche composed of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) was identified. Nestin-positive MSCs, identified by nestin expression, are essential components of the HSC niche. These cells are spatially associated with HSCs and adrenergic nerve fibers, and highly express genes involved in HSC maintenance. Nestin-positive MSCs can self-renew and expand in serial transplantations, and are capable of differentiating into osteoblasts, adipocytes, and chondrocytes. They are also required for HSC maintenance and homing in the bone marrow. Nestin-positive MSCs are distinct from osteoblasts and pre-osteoblasts, and are quiescent but metabolically active. They are regulated by the sympathetic nervous system and parathyroid hormone, and their function is essential for maintaining the HSC niche. The study reveals a novel partnership between two distinct somatic stem-cell types, indicating a unique niche in the bone marrow composed of heterotypic stem-cell pairs. The findings suggest that nestin-positive MSCs are bona fide MSCs capable of self-renewal in serial transplantations and contribute to the physiological formation of osteochondral lineages. The study also highlights the importance of nestin-positive MSCs in regulating HSC maintenance and progenitor homing.