In a Previous Life: Memory in Stem Cells

JENNA ZHANG

stem cellsFrom studying gray matter in Alzheimer’s to appreciating Mike Ross’ photographic memory in Suits, memory has long captured the imaginations of both scientists and the general public. Five years ago, Japanese biologists used a normal adult cell to create the first ever man-made human pluripotent stem cell. The breakthrough gave scientists the hope that we could eventually make pluripotent stem cells—those which can differentiate into any cell in the body—without having to harvest them from a human embryo. But can these artificial stem cells, called induced pluripotent stem (iPS) cells, remember their past?

Two separate research groups in Boston have found that the answer is yes. Dr. George Daley and his team at the Children’s Hospital compared iPS cells to another type of reprogrammed stem cell, somatic nuclear transfer cells (SCNT). By measuring patterns of DNA methylation—epigenetic markers that govern a cell’s unique functions—it became clear that iPS cells had not been reset as fully as the SCNT cells. Even after being artifically converted into stem cells, iPS cells still “remembered” their former identities as adult cells.

The question of whether iPS cells and embryonic cells are equivalent is still debated in the field. What this observation suggests is the importance in comparative studies to use high passage stem cells.

Not only does an iPS cell carry remnants of its past, but that memory can fade over time. Dr. Konrad Hochedlinger’s team at Massachusetts General Hospital observed that iPS cells that originally came from muscle cells, fibroblasts, and other types of cells carried a leftover imprint from their past form. But after ten to fifteen generations of cell replication, these different types of iPS cells became virtually the same: their patterns of DNA methylation, transcription, and histone modification were almost indistinguishable from each other.

If iPS cells have memories, then they would be imperfect replacements for stem cells derived directly from human embryos. Unless the memory has completely faded, an iPS cell would not be able to efficiently differentiate into other kinds of cells. Despite the limited flexibility, memories could still be used to streamline the development process. For example, young iPS cells derived from blood cells could be more efficiently differentiated into adult blood cells than iPS cells made from pancreatic cells. Hochedlinger concludes, “The question of whether iPS cells and embryonic cells are equivalent is still debated in the field. What this observation suggests is the importance in comparative studies to use high passage stem cells.” As further details emerge, it becomes more clear that an understanding of memory underlying iPS cells will be imperative in future studies within the field of stem cell research.

Jenna Zhang is a Brevia staff writer. She can be reached at jennazhang@college.harvard.edu.