Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age

Proceedings of the National Academy of Sciences of the United States of America - Tập 108 Số 50 - Trang 20012-20017 - 2011
Wendy W. Pang1, Elizabeth Price2, Debashis Sahoo3, Isabel Beerman4, William J. Maloney5, Derrick J. Rossi4, Stanley L. Schrier2, Irving L. Weissman3
1Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Stem Cell Research, and Department of Pathology, Stanford University, Stanford, CA 94305, USA.
2Department of Internal Medicine, Division of Hematology, and
3Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center for Stem Cell Research, and Department of Pathology,
4Immune Disease Institute, Harvard Medical School, Boston, MA 02115
5Department of Orthopaedic Surgery, Stanford University, Stanford, CA 94305; and

Tóm tắt

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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 108 Số 50

20012-20017

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