Microchimerism,
Human Health &
Evolution Project

Main project goals

This project aims to provide fundamental information about microchimerism at the cellular and molecular levels. Microchimerism is a complex biological phenomenon, and each microchimeric-host interaction is likely to be unique, influenced by factors such as host tissue, development stage, and underlying genomics. Our goal is to effectively characterize the dynamics of microchimeric hosts by identifying key parameters in microchimeric biology. Through this approach, we aim to gain a deeper understanding of the causes and consequences of microchimerism. In addition, we are committed to fostering a research environment that encourages expertise development and the advancement of methodologies to address new inquiries about microchimerism across different temporal and spatial contexts. By creating such an environment, we hope to facilitate innovative research and contribute to the growing knowledge in this field.
We have four overarching goals for this project:

  • understand how and where microchimeric cells are acquired in the host system and to screen for the potential of multiple-generation microchimeric cellular transfer,
  • investigate the consequences of microchimerism in health and disease, and to understand how microchimerism affects the development and function of host immune system dynamics,
  • establish a supportive team infrastructure for microchimeric research and
  • cultivate and integrate the field of microchimeric research.

The project aims to cultivate and revitalize the microchimerism community.

Approach

Our approach leverages principles from evolutionary theory and systems biology to study microchimerism in human health and disease. Microchimerism likely co-evolved with internal gestation in placental mammals around 100 million years ago, enabling the development of specialized functions of microchimeric cells within the host body. Therefore, we predict that microchimerism has evolutionary benefits, including enhanced reproductive success and survival. However, these benefits can also come at a cost, known as an evolutionary trade-off, when genetic interests diverge.

Maternal-fetal conflict theory, an extension of evolutionary theory, suggests that the mother and fetus share some common interests regarding reproductive success and survival. However, conflicts arise over resource distribution between the two organisms: maternal investment in the offspring’s health may lead to fitness benefits for both (Haig, 1993). Conversely, the offspring’s demand for resources may come at a cost to the mother. We propose that this framework can help resolve the paradox of microchimeric effects on host physiology. In other words, microchimerism should not be viewed as a simple dichotomy of helpful or harmful, but rather as a complex interaction between two genetically distinct individuals. Key factors such as tissue function (e.g., resource distribution tissue vs. immune priming), developmental timing (e.g., pregnancy, postpartum, fetal development), and alignment of genetic interests (e.g., overlap of maternal/paternal alleles) are crucial for understanding the biological consequences of microchimerism. Our expertise in genomics, immunology, cell biology, and evolution, combined with our proficiency in analytical technique development, and access to diverse tissue types at different developmental stages, allows for a more comprehensive systems biology approach to studying microchimerism.

Maternal-fetal conflict theory provides testable predictions for microchimerism

Natural selection operates to eliminate significant negative effects on both the maternal body and offspring. However, due to divergent genetic interests, natural selection also favors offspring that prioritize their own well-being and that of their own offspring over potential future siblings (Trivers, 1974). This leads to a conflict over the allocation of current resources within the maternal body.
According to maternal-fetal conflict theory, we predict that, on one hand, both hosts cooperate for survival, such as in wound healing and immune surveillance. On the other hand, there exists a conflict over resource transfers, where fetal cells are expected to become more extractive while maternal cells act to limit resources for the benefit of all current and future siblings. In other words, we anticipate that fetal microchimerism promotes the interests of the fetus, while maternal microchimerism promotes the interests of the mother as well as her current and future reproductive success.
Therefore, we further predict that genetic conflict will be observed in tissues crucial for fetal resource transfers into the maternal body (Boddy et al., 2015), such as the thyroid (for heat regulation), breast tissue (for lactation), brain (for attachment and bonding), and ovaries (for reducing sibling conflict). We expect active migration and differentiation of microchimeric cells to these maternal body sites and tissues to support proper organ function.
Regarding maternal microchimerism, we predict that the maternal response will “dampen” or reduce offspring demands regarding hunger or sleep needs (Haig, 2014), while also providing an immunological benefit for enhanced survival of current offspring. Thus, we anticipate the active migration of maternal microchimeric cells to the pancreas (for insulin regulation), stomach (for ghrelin regulation), as well as lymph nodes and bone marrow.
Furthermore, we predict that this conflict will manifest in maternal-fetal cross talk between microchimeric cells and the host immune system. We would expect to observe higher conflict in cases where there are greater human leukocyte antigen (HLA) mismatches between maternal and paternal alleles.

Literature

  • Haig, D. (1993). Genetic conflicts in human pregnancy. The Quarterly Review of Biology, 68(4), 495–532.
  • Haig, D. (2014). Does microchimerism mediate kin conflicts? Chimerism, 5(2).
    Trivers, R. L. (1974).
  • Parent-Offspring Conflict. American Zoologist, 14(1), 249–264.