Epigenomic Profiling of Young and Aged HSCs Reveals Concerted Changes during Aging that Reinforce Self-Renewal

被引：484

作者：

Sun, Deqiang ^{[2
,3
]}

Luo, Min ^{[1
]}

Jeong, Mira ^{[1
]}

Rodriguez, Benjamin ^{[2
,3
]}

Xia, Zheng ^{[2
,3
]}

Hannah, Rebecca ^{[4
,5
]}

Wang, Hui ^{[6
]}

Le, Thuc ^{[7
,8
]}

Faull, Kym F. ^{[7
,8
]}

Chen, Rui ^{[6
]}

Gu, Hongcang ^{[10
]}

Bock, Christoph ^{[10
,11
]}

Meissner, Alexander ^{[10
]}

Goettgens, Berthold ^{[4
,5
]}

Darlington, Gretchen J. ^{[9
]}

Li, Wei ^{[2
,3
]}

Goodell, Margaret A. ^{[1
,2
,3
]}

机构：

[1] Baylor Coll Med, Stem Cells & Regenerat Med Ctr, Dept Pediat & Mol & Human Genet, Houston, TX 77030 USA

[2] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[4] Univ Cambridge, Dept Dermatol, Cambridge Inst Med Res, Cambridge CB2 0XY, England

[5] Univ Cambridge, Wellcome Trust & MRC Cambridge Stem Cell Inst, Cambridge CB2 0XY, England

[6] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[7] Univ Calif Los Angeles, Pasarow Mass Spectrometry Lab, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA

[8] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Los Angeles, CA 90095 USA

[9] Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA

[10] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[11] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02142 USA

来源：

CELL STEM CELL | 2014年 / 14卷 / 05期

基金：

英国生物技术与生命科学研究理事会;

关键词：

HEMATOPOIETIC STEM-CELLS; DNA METHYLATION LANDSCAPE; LIFE-SPAN; TGF-BETA; TET2; DIFFERENTIATION; PROLIFERATION; GROWTH; MUTATIONS; DNMT3A;

D O I：

10.1016/j.stem.2014.03.002

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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-beta 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.

引用

页码：673 / 688

页数：16

共 64 条

[1] Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging [J].