Age-related transcription levels of KU70, MGST1 and BIK in CD34+hematopoietic stem and progenitor cells

作者：Prall Wolf C^*; Czibere Akos; Jaeger Marcus; Spentzos Dimitrios; Libermann Towia A; Gattermann Norbert; Haas Rainer; Aivado Manuel

来源：Mechanisms of Ageing and Development, 2007, 128(9): 503-510.

DOI：10.1016/j.mad.2007.06.008

• cDNA macroarray
• gene expression
• aging
• HSC
• hematopoietic stem cells
• oncogenesis

Despite the known longevity of human hematopoietic stem and progenitor cells (HSC), numerous functional impairments of these cells can be observed in an age-dependent manner. However, the molecular alterations associated with aging of HSC are largely unknown. Therefore, we scrutinized gene expression patterns of HSC from newborn, young and old healthy donors. CD34+ HSC were isolated via immuno-magnetic separation and evaluated by FACS analysis. We performed cDNA macroarray analyses on a first set of CD34+ samples (n = 13). We found the genes encoding KU-antigen 70 kD (KU70), microsomal glutathione S-transferase 1 (MGSTI) and BCL2-interacting killer (BIK) to possess agerelated mRNA expression levels. KU70 is a DNA repair gene and part of the DNA-dependent protein kinase (DNA-PK) complex. Its expression was negatively correlated with donor age showing highest expression levels in newborn, 2.6-fold lower levels in young and 6.3-fold lower levels in old donors. The transcription levels of MGSTI, a gene protecting against oxidative stress, progressively increased with age. Expression was lowest in newborn, 2.6-fold higher in young and 4.3-fold higher in old donors. BIK is a proapoptotic gene and its expression was positively correlated with donor age: lowest in newborn, 1.8-fold higher in young and 4. 1 -fold higher in old donors. These findings were confirmed with an independent, second set of CD34+ samples (n = 16) by means of quantitative real-time RT-PCR. Elucidation of age-dependent molecular alterations in healthy HSC facilitate a better understanding of functional impairments in hematopoiesis and may become valuable for anti-aging drug development and the emerging field of regenerative medicine.

• 出版日期2007-9