| Literature DB >> 24792119 |
Deqiang Sun1, Min Luo2, Mira Jeong2, Benjamin Rodriguez1, Zheng Xia1, Rebecca Hannah3, Hui Wang4, Thuc Le5, Kym F Faull5, Rui Chen4, Hongcang Gu6, Christoph Bock7, Alexander Meissner6, Berthold Göttgens3, Gretchen J Darlington8, Wei Li9, Margaret A Goodell10.
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.Entities:
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Year: 2014 PMID： 24792119 PMCID： PMC4070311 DOI： 10.1016/j.stem.2014.03.002
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633