Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells

• DOI: 10.1084/jem.20111490
• Publication Date: 2011-11-22T07:39:35Z
• Authors: Brad Dykstra; Sandra Olthof; Jaring Schreuder; Martha Ritsema; Gerald de Haan
• Keywords: Homing (biology); Hematopoietic stem cell

Hematopoietic stem cell (HSC) populations change with aging, but the extent to which this is caused by qualitative versus quantitative alterations in HSC subtypes unclear. Using clonal assays, study we show that aging compartment undergoes both and changes. We observed a variable increase of pool size age, accompanied accumulation predominantly myeloid-biased HSCs regenerate substantially fewer mature progeny than young exhibit reduced self-renewal activity as measured long-term secondary transplantation. Old had twofold reduction marrow-homing efficiency similar decrease functional frequency using transplantation assays. Similarly, old seeding significantly delayed proliferative response compared stromal co-cultures were indistinguishable suspension cultures. these defects are characteristics most or all not indicative nonfunctional subset cells express markers. Furthermore, demonstrate properties can be generated directly from extended serial transplantation, consistent possibility they arise through process cellular aging.