Accumulating mitochondrial DNA mutations drive premature hematopoietic aging phenotypes distinct from physiological stem cell aging.

Summary, in English

Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understanding the aging process. Here, using a model carrying a proofreading-defective mitochondrial DNA polymerase, we demonstrate hematopoietic defects reminiscent of premature HSC aging, including anemia, lymphopenia, and myeloid lineage skewing. However, in contrast to physiological stem cell aging, rapidly accumulating mitochondrial DNA mutations had little functional effect on the hematopoietic stem cell pool, and instead caused distinct differentiation blocks and/or disappearance of downstream progenitors. These results show that intact mitochondrial function is required for appropriate multilineage stem cell differentiation, but argue against mitochondrial DNA mutations per se being a primary driver of somatic stem cell aging.

• Författare: Gudmundur Norddahl; Kees-Jan Pronk; Martin Wahlestedt; Gerd Sten; Jens Nygren; Amol Ugale; Mikael Sigvardsson; David Bryder
• Avdelning/ar: Immunology; Institutionen för experimentell medicinsk vetenskap; Stamcellscentrum (SCC); Hematopoietic and immunologic developement; StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
• Publiceringsår: 2011
• Språk: Engelska
• Sidor: 499-510
• Publikation/Tidskrift/Serie: Cell Stem Cell
• Volym: 8
• Issue: 5
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/21549326?dopt=Abstract; http://dx.doi.org/10.1016/j.stem.2011.03.009
• Dokumenttyp: Artikel i tidskrift
• Förlag: Cell Press
• Ämne: Cell Biology
• Status: Published
• Forskningsgrupp: Immunology; Hematopoietic and immunologic developement
• ISBN/ISSN/Övrigt: ISSN: 1934-5909