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Cell Stem Cell. 2014 May 1;14(5):673-88. doi: 10.1016/j.stem.2014.03.002.

Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal.

Author information

1
Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
2
Stem Cells and Regenerative Medicine Center, Department of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
3
Department of Hematology, Cambridge Institute for Medical Research and Wellcome Trust and MRC Cambridge Stem Cell Institute, Cambridge University, Hills Road, CB2 0XY Cambridge, UK.
4
Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
5
Pasarow Mass Spectrometry Laboratory, Department of Psychiatry and Biobehavioral Sciences and the Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
6
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
7
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02142, USA.
8
Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
9
Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: wl1@bcm.edu.
10
Stem Cells and Regenerative Medicine Center, Department of Pediatrics and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: goodell@bcm.edu.

Abstract

To investigate the cell-intrinsic aging mechanisms that erode the function of somatic stem cells during aging, we have conducted a comprehensive integrated genomic analysis of young and aged cells. We profiled the transcriptome, DNA methylome, and histone modifications of young and old murine hematopoietic stem cells (HSCs). Transcriptome analysis indicated reduced TGF-β signaling and perturbation of genes involved in HSC proliferation and differentiation. Aged HSCs exhibited broader H3K4me3 peaks across HSC identity and self-renewal genes and showed increased DNA methylation at transcription factor binding sites associated with differentiation-promoting genes combined with a reduction at genes associated with HSC maintenance. Altogether, these changes reinforce HSC self-renewal and diminish differentiation, paralleling phenotypic HSC aging behavior. Ribosomal biogenesis emerged as a particular target of aging with increased transcription of ribosomal protein and RNA genes and hypomethylation of rRNA genes. This data set will serve as a reference for future epigenomic analysis of stem cell aging.

PMID:
24792119
PMCID:
PMC4070311
DOI:
10.1016/j.stem.2014.03.002
[Indexed for MEDLINE]
Free PMC Article

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