Molecular pathways regulating the self-renewal of hematopoietic stem cells

Hematopoietic stem cells (HSC) self-renew throughout life, but the molecular mechanisms by which this process occurs and is regulated are imprecisely understood. We review the published data from overexpression and knockout studies describing genes that influence stem cell self-renewal, including transcription factors, cell cycle regulators, and genes that influence chromosome structure. One model suggesting how some of these disparate classes of molecular regulators might be integrated is presented, focusing on the role of G1/S progression in the developmental switch toward stem cell self-renewal vs differentiation. Experimental exploration of this model and other related hypotheses will hopefully lead to a more complete description of HSC self-renewal and its regulation, both in normal physiology and in applied therapeutics.