Diagram showing input from multiple signals that affect expansion of HSCs. Proliferation and differentiation of HSCs are regulated by the interplay of stimulatory and inhibitory modulators released by neighboring cells that inhabit the HSC niche within the bone marrow and other cell types within the hematolymphoid compartment. Synthetic molecules utilized to promote ex vivo expansion of HSCs are also depicted. Addition of stimulatory molecules combined with reduction in abundance of inhibitory factors represents a promising strategy to induce in vitro proliferation while maintaining HSCs in an undifferentiated state. Abbreviations used: AhR: aryl hydrocarbon receptor, Angpt: angiopoietin, Angptls: angiopoietin-like proteins, CCL: chemokine ligand, CXCL10: chemokine ligand 10, Hh: hedgehog, Hox: homeobox, IL: interleukin, PF4: platelet factor 4, PGE2: prostaglandin E2, SCF: stem cell factor, SR1: StemRegenin, TGF-β: transforming growth factor beta, TNF: tumor necrosis factor, TPO: thrombopoietin.