Gene Expression Among Individual Microchimeric Maternal Cells
Principal Investigator: Sing Sing Way, MD, PhD
Each of us has a biological mother. And while we are physically separated from our mothers now, each of us still contain our mother’s cells inside of us. Likewise, each of our mothers contains our cells inside of them. These genetically foreign cells ubiquitously transferred during pregnancy, and retained in mothers and offspring, are called microchimeric cells. Although the existence of these cells is now generally accepted, we do not know much about what they do and how they work.
We recently showed that maternal cells retained in offspring are not accidental souvenirs of pregnancy, but in fact, deliberately placed to ensure the success of a future pregnancy. These groundbreaking findings were revealed after developing the first experimental approaches for depleting these cells, and evaluating the impacts on reproductive fitness in pre-clinical pregnancy models. Now that we know one aspect of nature’s intent in preserving the retention of genetically foreign maternal cells in human babies, and offspring across all placental mammalian species, it is even more important to understand how they escape rejection and protect against pregnancy complications.
A major limitation in understanding how these cells work is their exceptional rarity, estimated at one in every million cells in our bodies. However, being rare does not mean these cells are not important. We have developed cutting-edge tools to consistently isolate these exceptionally rare cells from individual tissues. Nonetheless, the relatively few cells we can obtain from individual tissues, and their potential heterogeneity in phenotype and function, still precludes their analysis using standard analytical tools based on protein expression.
Therefore, our goal in this CpG pilot grant is to use single cell gene expression tools to investigate in an unbiased fashion the molecules that microchimeric cells express within individual tissues and across multiple tissues. These results likely will revolutionize how we currently think about immunology, and open up exciting new ways for us to think about common immunological problems such as autoimmunity, cancer and transplantation.