Various embodiments provide methods and related compositions for increasing the population size of hematopoietic stem cells (HSCs) in patients that may benefit from reconstitution of stem cells and/or differentiated cells of the blood lineage. The present methods enable the production of HSCs ex vivo and in vivo by reducing latexin expression and/or latexin activity within HSC exposed to various antagonists. Inhibition of latexin expression and/or latexin activity by various antagonists can promote HSC proliferation and/or inhibit HSC apoptosis. Antagonists that can reduce latexin expression and/or latexin activity can be utilized to regenerate endogenous HSCs within patients affected with disorders, diseases, cancers, or therapies for such conditions, that result in the depletion or reduction in HSCs