Microchimerism (MC) is the phenomenon where cells originating from two genetically different organisms exist in one individual. MC is common in mammals. Numerous observations suggest that MC may have large impacts on human health, but how MC is enabled and develops and affects health remains obscure. What distinguishes one individual from another genetically seems evident. But what is hereditary if you find cells from your mother integrated into your own tissues? Can you potentially pass these on to your own children? How do these cells affect immune system development? MC is potentially a major factor in mammalian epigenetic inheritance. Our international cross-interdisciplinary team includes experts in immunology, evolutionary biology, genomics, analytical chemistry, and cell biology. We will bring this expertise to bear on broad and deep questions in how MC occurs and affects mammalian biology. We will phenotype host-MC relationships in a variety of evolutionarily relevant contexts, including various tissues, immune system dynamics, and cell tracking across generations. We will use cutting edge technology, including whole body microtoming, in situ- and single cell sequencing, functional analyses, and longitudinal analyses to understand the causes and consequences of MC. This work will produce at least 15 peer-reviewed papers and book chapters and 15 scientific conference presentations and lectures. We will also train at least 10 early- and mid-career scientists and implement a cross-lab exchange program, and expect this project will create significant new interest in the study of MC. This is a high risk/high reward project with potential to fundamentally change our understanding of MC-mediated epigenetic inheritance. The co-evolution of MC and its effects on maternal and subsequent generation immune function has major implications for immunity and immune tolerance during pregnancy and after transplantation, and in relation to cancer and autoimmune disorders.
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