Model of HSC niche regulation in steady state. (A) Perivascular niches harboring active HSCs that regenerate the hematopoietic system. Active HSCs are in contact with perivascular nestin⁺ MSCs and sinusoidal endothelial cells. Both MSCs and sinusoidal endothelial cells express SDF-1, transmembrane SCF, and VCAM-1 that retain HSCs within the niche via adhesive and chemotactic interactions. (B) Endosteal niches harboring quiescent HSCs. Quiescent HSCs are in contact with nestin⁺ MSCs or osteoprogenitors or both. (C) Interactions between niches cells, HSCs, and adrenergic neurons. CD68⁺ CD169⁺ macrophages and osteomacs forming support function of nestin⁺ MSCs, osteoprogenitors and osteoblasts which in turn maintain HSCs in steady state (stimulating feed-back illustrated by green arrow). Sympathetic β3 adrenergic nerves inhibit SDF-1 secretion by MSCs and osteoblasts after a circadian pulse (negative pulse illustrated by dotted red bars).