Age and ancestry affect production of induced pluripotent stems cells

2020

Challenge

Scientists can turn fully mature cells into induced pluripotent stem cells (iPSCs), which can then develop into any type of specialized cell, including skin, muscle, and brain cells. This process enables researchers to grow unique and personalized cells in the lab that exhibit specific disease-related traits. However, while we know that there is substantial genomic variation across individuals and major racial ancestral groups, this diversity is not reflected in the cell cultures used in many genomic studies. This “missing diversity” makes it harder to figure out how genetic variability can influence biological processes, including the ability of iPSCs to develop into more specialized cells.

Advance

IRP researchers led by Trevor K. Archer, Ph.D., transformed human skin cells into iPSCs and examined how genetic factors related and unrelated to the cell donors’ age, sex, and ancestry affected the number of new cell colonies the scientists were able to grow from each cell line. They found that iPSCs derived from the cells of older individuals generated fewer new colonies, while African American ancestry was associated with a greater number of new colonies. Sex did not appear to have a significant effect. Finally, genes associated with the ability to successfully turn the skin cells into iPSCs included some involved in wound healing and cancer.

Impact

The diversity of the volunteers who donated cells for the study allowed for the identification of a greater number of genes involved in creating iPSCs than could have been achieved using a less diverse group. As a result, the study demonstrates that genetic variation can impact the ability of cells to become iPSCs and highlights the value of using research and disease models from diverse backgrounds to understand and promote human health.

Publications

Bisogno LS, Yang J, Bennett BD, Ward JM, Mackey LC, Annab LA, Bushel PR, Singhal S, Schurman SH, Byun JS, Napoles AM, Perez-Stable EJ, Fargo DC, Gardner K, Archer TK. (2020). Ancestry-dependent gene expression correlates with reprogramming to pluripotency and multiple dynamic biological processes. Sci. Adv. Nov 20;6(47):eabc3851. doi: 10.1126/sciadv.abc3851.

Mackey LC, Annab LA, Yang J, Rao B, Kissling GE, Schurman SH, Dixon D, Archer TK. (2018). Epigenetic enzymes, age, and ancestry regulate the efficiency of human iPSC reprogramming. Stem Cells. Nov;36(11):1697-1708. doi: 10.1002/stem.2899.