title: Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age.
abstract: In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. Though the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have been incompletely characterized. To elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated immunophenotypic HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged immunophenotypic human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared with young HSC. Gene expression profiling revealed that aged immunophenotypic human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, developmental potential, and gene expression profile of human HSC are similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.
authors: Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Stem Cell Research, and Department of Pathology, Stanford University, Stanford, CA 94305, USA. wendy.pang@stanford.edu
authors: Wendy W
authors: WW
authors: Pang
authors: Elizabeth A
authors: EA
authors: Price
authors: Debashis
authors: D
authors: Sahoo
authors: Isabel
authors: I
authors: Beerman
authors: William J
authors: WJ
authors: Maloney
authors: Derrick J
authors: DJ
authors: Rossi
authors: Stanley L
authors: SL
authors: Schrier
authors: Irving L
authors: IL
authors: Weissman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008875:Middle Aged; D022423:Myeloid Cells / Q000166:cytology / Q000378:metabolism; D055815:Young Adult