U.S. Department of Health and Human Services

New Insight into the Mouse Blood Stem Cell Aging Process

​Recent research identified changes in blood (hematopoietic) stem cells (HSCs) that may contribute to age-associated loss of function. The HSC, a type of adult stem cell, holds great promise for future biomedical applications because of its ability to self-renew and develop into any kind of blood cell. However, previous research has shown that as the HSC ages, its capacity to develop into different types of blood cells diminishes. The mechanism(s) responsible for this change is not well defined.

New research has provided insight into the HSC’s aging process by systematically evaluating the gene expression (whether genes are turned “off” or “on”) in cells from both young and old male mice. For this study, the researchers used several techniques, including a process called transcriptome analysis, to determine the extent to which genes are on or off depending on the age of the HSCs. They also studied chemical modifications along the genome that affect gene expression. The genome is made up of DNA, a long, winding molecule that contains the instructions, in the form of genes, needed to build and maintain cells. For these instructions to be carried out, DNA must be transcribed into corresponding molecules of RNA, referred to as transcripts. A transcriptome is a collection of all the transcripts present in a given cell. Often researchers can count the number of different types of transcripts in the transcriptome to determine the level of activity of different genes, also called gene expression, in a certain cell or tissue type. In humans and other multi-cell creatures, nearly every cell contains the same genes, but different cells show different patterns of gene expression. These differences in gene expression are responsible for the many different properties and behaviors of various cells and tissues as they experience health, normal aging, and disease. Cells also make various modifications along the genome, such as adding chemical “markers” to their DNA. Called “epigenetic” changes, these modifications affect gene expression.

A new analysis of mouse HSC transcriptomes and various epigenetic markers identified many genes that were expressed differently by old and young mice. Researchers found, for instance, that genes regulated by a growth factor called TGF-β showed differences in expression between young and old HSC cells. This finding suggests that there is less signaling by TGF-β in older cells. Previous research has shown that TGF-β helps control the growth and proliferation of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement, and the self-destruction of cells. In addition, the researchers confirmed and extended previous studies by identifying epigenetic changes in young versus old HSCs that are consistent with the aging HSCs’ inability to develop into other types of blood cells. 

Taken together, this study provides a comprehensive analysis of the genomic properties of young and old mouse HSCs and suggests how changes in the stem cell during aging promotes self-renewal and hinders HSCs’ ability to transition into other types of blood cells. This research provides new insight into the aging process and may be the basis for future treatments for aging-related disorders.

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. Epigenomic profiling of young and aged HSCs reveals concerted changes during aging that reinforce self-renewal. Cell Stem Cell 14: 673-688, 2014.