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Cell Stem Cell DOI:10.1016/j.stem.2014.03.002

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

Publication TypeJournal Article
Year of Publication2014
AuthorsSun, D, Luo, M, Jeong, M, Rodriguez, B, Xia, Z, Hannah, R, Wang, H, Le, T, Faull, KF, Chen, R, Gu, H, Bock, C, Meissner, A, Göttgens, B, Darlington, GJ, Li, W, Goodell, MA
JournalCell Stem Cell
Volume14
Issue5
Pages673-88
Date Published2014 May 01
ISSN1875-9777
KeywordsAnimals, Cell Aging, Cell Differentiation, Cells, Cultured, Chromatin Immunoprecipitation, Epigenomics, Hematopoietic Stem Cells, Male, Mice, Transforming Growth Factor beta
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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S1934-5909(14)00096-4
DOI10.1016/j.stem.2014.03.002
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/24792119?dopt=Abstract

Alternate JournalCell Stem Cell
PubMed ID24792119
PubMed Central IDPMC4070311
Grant ListCA125123 / CA / NCI NIH HHS / United States
T32 HD007032 / HD / NICHD NIH HHS / United States
K99 DK084259 / DK / NIDDK NIH HHS / United States
Z01 AG000183 / AG / NIA NIH HHS / United States
R56 DK092883 / DK / NIDDK NIH HHS / United States
T32 AG000183 / AG / NIA NIH HHS / United States
T32 MH019384 / MH / NIMH NIH HHS / United States
AI07495 / AI / NIAID NIH HHS / United States
DK056338 / DK / NIDDK NIH HHS / United States
DK092883 / DK / NIDDK NIH HHS / United States
R01 AG028865 / AG / NIA NIH HHS / United States
G0900729/1 / / National Centre for the Replacement, Refinement and Reduction of Animals in Research / United Kingdom
AG036562 / AG / NIA NIH HHS / United States
DK084259 / DK / NIDDK NIH HHS / United States
12765 / / Cancer Research UK / United Kingdom
T32 AI007495 / AI / NIAID NIH HHS / United States
R21 AG034451 / AG / NIA NIH HHS / United States
P50 CA126752 / CA / NCI NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
G0900951 / / Medical Research Council / United Kingdom
P30 DK056338 / DK / NIDDK NIH HHS / United States
AG000183 / AG / NIA NIH HHS / United States
T32 MH19384-14 / MH / NIMH NIH HHS / United States
CA126752 / CA / NCI NIH HHS / United States
T32-HD007032 / HD / NICHD NIH HHS / United States
RC2 AG036562 / AG / NIA NIH HHS / United States
HG007538 / HG / NHGRI NIH HHS / United States
AG288652 / AG / NIA NIH HHS / United States
R01 HG007538 / HG / NHGRI NIH HHS / United States
R00 DK084259 / DK / NIDDK NIH HHS / United States
R01 DK092883 / DK / NIDDK NIH HHS / United States