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Cell Intrinsic Alterations Underlie Hematopoietic Stem Cell Aging

Rossi, Derrick J. ; Bryder, David ; Zahn, Jacob M. ; Ahlenius, Henrik ; Sonu, Rebecca ; Wagers, Amy J. ; Weissman, Irving L.

Proceedings of the National Academy of Sciences - PNAS, 2005-06, Vol.102 (26), p.9194-9199 [Revista revisada por pares]

United States: National Academy of Sciences

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Cell Intrinsic Alterations Underlie Hematopoietic Stem Cell Aging
Autor: Rossi, Derrick J. ; Bryder, David ; Zahn, Jacob M. ; Ahlenius, Henrik ; Sonu, Rebecca ; Wagers, Amy J. ; Weissman, Irving L.
Materias: Aging ; Animals ; B lymphocytes ; Basic Medicine ; Biological Sciences ; Cell Lineage ; Cell Separation ; Cell Transformation, Neoplastic ; Cell Transplantation ; Cells ; Cellular Senescence ; Clinical Medicine ; Down-Regulation ; Flow Cytometry ; Gene Expression Regulation ; Genes ; Genome ; Hematopoiesis ; Hematopoietic stem cells ; Hematopoietic Stem Cells - cytology ; Immune system ; Immunologi inom det medicinska området ; Immunology in the medical area ; Klinisk medicin ; Leukemia ; Leukemia - metabolism ; lineage potential ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicinska och farmaceutiska grundvetenskaper ; Mice ; Mice, Inbred C57BL ; microarray ; Neurologi ; Neurology ; Oligonucleotide Array Sequence Analysis ; ontogeny ; Progenitor cells ; Reverse Transcriptase Polymerase Chain Reaction ; Software ; Stem cells ; Stem Cells - cytology ; Stem Cells - metabolism ; T lymphocytes ; Transplantation ; Up regulation
Es parte de: Proceedings of the National Academy of Sciences - PNAS, 2005-06, Vol.102 (26), p.9194-9199
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I.L.W. was a member of the scientific advisory board of Amgen and owns significant Amgen stock. He cofounded and consulted for Systemix, is a cofounder and director of Stem Cells, Inc., and recently cofounded Cellerant, Inc. None of these companies is involved in aging research.
Abbreviations: HSC, hematopoietic stem cell; LT-HSC, long-term HSC; BM, bone marrow; CLP, common lymphoid progenitor; KLS, c-kit positive, lineage negative, and Sca-1 positive; CMP, common myeloid progenitor; MEP, megakaryocyte-erythrocyte progenitor; GMP, granulocyte-macrophage progenitor; qRT-PCR, quantitative RT-PCR.
Contributed by Irving L. Weissman, April 25, 2005
To whom correspondence may be addressed. E-mail: drossi@stanford.edu or irv@stanford.edu.
D.J.R. and D.B. contributed equally to this work.
Descripción: 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.
Editor: United States: National Academy of Sciences
Idioma: Inglés

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Cell Intrinsic Alterations Underlie Hematopoietic Stem Cell Aging

Rossi, Derrick J. ; Bryder, David ; Zahn, Jacob M. ; Ahlenius, Henrik ; Sonu, Rebecca ; Wagers, Amy J. ; Weissman, Irving L.

United States: National Academy of Sciences

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