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

Deqiang Sun, Min Luo, Mira Jeong, Benjamin Rodriguez, Zheng Xia, Rebecca Hannah, Hui Wang, Thuc Le, Kym F. Faull, Rui Chen, Hongcang Gu, Christoph Bock, Alexander Meissner, Berthold Göttgens, Gretchen J. Darlington, Wei Li, Margaret A. Goodell

Research output: Contribution to journalArticle

251 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)673-688
Number of pages16
JournalCell Stem Cell
Volume14
Issue number5
DOIs
StatePublished - May 1 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Sun, D., Luo, M., Jeong, M., Rodriguez, B., Xia, Z., Hannah, R., Wang, H., Le, T., Faull, K. F., Chen, R., Gu, H., Bock, C., Meissner, A., Göttgens, B., Darlington, G. J., Li, W., & Goodell, M. A. (2014). Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. Cell Stem Cell, 14(5), 673-688. https://doi.org/10.1016/j.stem.2014.03.002