Cell intrinsic alterations underlie hematopoietic stem cell aging

Research output: Contribution to journalArticle

Abstract

Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology
  • Immunology in the medical area

Keywords

  • microarray, ontogeny, lineage potential, leukemia
Original languageEnglish
Pages (from-to)9194-9199
JournalProceedings of the National Academy of Sciences
Volume102
Issue number26
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes