Aging of murine hematopoietic stem cells

Hematopoietic stem cells (HSCs) are unique in their ability to self-renew and differentiate into all mature blood lineages. The equilibrium between these processes is crucial for tissue maintenance during the lifetime of the organism. However, with age the functionality of HSCs declines, resulting indevelopment of anemias, deficiencies of immune response, and increased risk of hematopoietic malignancies. Aged HSCs are characterized by preferential differentiation toward myeloid lineage, impaired self-renewal, and engraftment. Recent evidence provides clues to the understanding of these processeson cellular and molecular levels. Key components contributing to stem cell aging are shifts in the transcriptome and epigenome, accompanied by dysfunction of DNA repair pathways. In this chapter we will focus on studies and conceptual models of murine HSC aging.