Title | Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Sun, 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 |
Journal | Cell Stem Cell |
Volume | 14 |
Issue | 5 |
Pagination | 673-88 |
Date Published | 2014 May 01 |
ISSN | 1875-9777 |
Keywords | Animals, Cell Differentiation, Cells, Cultured, Cellular Senescence, 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. |
DOI | 10.1016/j.stem.2014.03.002 |
Alternate Journal | Cell Stem Cell |
PubMed ID | 24792119 |
PubMed Central ID | PMC4070311 |
Grant List | CA125123 / CA / NCI NIH HHS / United States AG036562 / AG / NIA NIH HHS / United States DK084259 / DK / NIDDK NIH HHS / United States P30 CA125123 / CA / NCI NIH HHS / United States P30 DK056338 / DK / NIDDK NIH HHS / United States T32 MH19384-14 / MH / NIMH NIH HHS / United States RC2 AG036562 / AG / NIA NIH HHS / United States R01 HG007538 / HG / NHGRI NIH HHS / United States T32 HD007032 / HD / NICHD NIH HHS / United States MC_PC_12009 / MRC_ / Medical Research Council / United Kingdom K99 DK084259 / DK / NIDDK 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 / NC3RS_ / National Centre for the Replacement, Refinement and Reduction of Animals in Research / United Kingdom Z01 AG000183 / ImNIH / Intramural NIH HHS / United States T32 AI007495 / AI / NIAID NIH HHS / United States 12765 / CRUK_ / Cancer Research UK / United Kingdom R21 AG034451 / AG / NIA NIH HHS / United States P50 CA126752 / CA / NCI NIH HHS / United States AG000183 / AG / NIA NIH HHS / United States G0900951 / MRC_ / Medical Research Council / United Kingdom CA126752 / CA / NCI NIH HHS / United States T32-HD007032 / HD / NICHD NIH HHS / United States HG007538 / HG / NHGRI NIH HHS / United States AG288652 / AG / NIA NIH HHS / United States R00 DK084259 / DK / NIDDK NIH HHS / United States R01 DK092883 / DK / NIDDK NIH HHS / United States |
Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal.
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