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

By Deqiang Sun, Min Luo, M. Jeong, Benjamin Rodriguez, Zheng Xia, Rebecca Hannah, Hui Wang, Thuc M. Le, K. Faull, Rui Chen and 7 more. Cell Stem Cell, 2014

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SUMMARY 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 TGFβ 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. Together 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 dataset will serve as a reference for future epigenomic analysis of stem cell aging.

Subfields: Aging, Molecular Biology, Pediatrics, Perinatology and Child Health

View Paper: https://www.semanticscholar.org/paper/ecab3122436a6e1dc7e9729b276e29b654a63476

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Citations in the corpus

A single-cell resolution map of mouse hematopoietic stem and progenitor cell differentiation. (2016, background): “Interestingly, however, conventional expression profiling of HSCs from old mice when coupled with epigenetic analysis had already suggested that in old HSCs, the transcriptomic and epigenetic landscape promotes HSC self-renewal at the expense of differentiation.(52) Future exploitations of the singl”
Single-cell RNA-seq reveals changes in cell cycle and differentiation programs upon aging of hematopoietic stem cells (2015, background): “G1 phase is a sensitive period during which cell fate decisions are made (Takahashi et al. 1995; Sherr 2000; Calegari and Huttner 2003; Massague 2004; Pauklin and Vallier 2013).”
Gene co-expression analysis for functional classification and gene–disease predictions (2017, background): “This is supported by the observation that the expression of cell cycle genes associated with ageing decreased in the analysis of non-cell-type-specific data [169].”
Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials (2019, background): “Normal dynamic changes in DNA methylation and demethylation based on altered expression of enzymes have been known to be associated with aging.(11,12) However, inappropriate methylation of DNA can result in multiple diseases, including inflammatory diseases, precancerous lesions, and cancer.”
DNA Methylation in Cancer and Aging. (2016, background): “Whole-genome bisulfite analysis indicates that this aging process is associated with typical de novo and demethylation events normally found in tumors (6, 14), and there is a good possibility that these alterations in methylation actually play a role in promoting stem cell renewal and inhibiting dif”