Microchimerism and Kinship: Evolutionary Conflict, Tolerance, and Cellular Competition
Microchimerism situates evolutionary cooperation and conflict within the bodies of mammals, embedding kin-selected interests into maternal and offspring tissues. Cellular exchange during gestation introduces genetically distinct lineages whose fitness interests may align or diverge depending on relatedness, timing, and reproductive context. Evolutionary models predict that offspring-derived cells residing in maternal tissues could influence resource allocation, interbirth intervals, and maternal physiology in ways that enhance their own genetic success, while maternal cells introduced during fetal immune development may shape tolerance with fewer long-term costs. This temporal asymmetry suggests distinct immunological and fitness consequences for fetal versus maternal microchimerism. Emerging evidence that newly acquired fetal microchimeric populations displace older ones challenges assumptions of cumulative tolerance and reframes persistence as a dynamic arena of cellular competition. Mathematical modeling further conceptualizes displacement as an adaptive strategy shaped by conflicting selective pressures between mothers and sequential offspring. This session covers microchimerism as an evolutionary mechanism balancing reproductive tolerance, immunological surveillance, and intergenerational conflict.
Wednesday, 27.05.2026, Day 1
Time: 16:15 – 17:30
Evolutionary perspectives on microchimerism
Amy M. Boddy
Department of Anthropology, University of California Santa Barbara
Fetal microchimerism has been associated with both positive and negative effects on maternal health. These mixed effects may stem from an evolutionary tension: mothers and their offspring have shared interests in some areas but conflicting interests in others, a dynamic known as maternal-fetal conflict. From an evolutionary perspective, fetal cells may function similarly to the placenta. Just as the placenta transfers resources from mother to baby during pregnancy, fetal cells that remain in maternal tissues after birth may continue to help transfer resources to the offspring. This resource transfer can benefit both mother and child, or it can represent the fetus “pushing” for more than what’s optimal for the mother’s health, creating conflict over how resources are allocated. Depending on the mother’s specific circumstances and health needs, these fetal cells may help with maternal bodily maintenance (such as wound healing) or manipulate maternal physiology in ways that favor the offspring. We propose that fetal cells play important roles in sustaining maternal investment in offspring after birth by influencing key systems like milk production, body temperature regulation, and mother-infant bonding.
Fetal Microchimeric Cells: Today’s Enemies, Tomorrow’s Friends
Francisco Ubeda
Francisco Ubeda1 and Geoff Wild2
Affiliations: 1. Royal Holloway Univesity of London (UK); 2. Western University (Canada)
Detection and transcriptional profiling of microchimerism in the brain using snRNAseq data reveals prevalent microchimerism and diversity of maternal cell fates
Ashley McDonough
Ashley McDonough1, Sami B Kanaan2, Reza Behboudi4, Coline Gentil3, Francesca Urselli2, Dan Geraghty2, Dan Eisenberg5, Haynes Heaton4, Jeff Ojemann6,7, Jonathan R Weinstein1,6, J Lee Nelson2,8
1 Department of Neurology, University of Washington;
2 Fred Hutchinson Cancer Center;
3 Immunoconcept, University of Bourdeaux, France;
4 Auburn University;
5 Department of Anthropology, University of Washington,
6 Department of Neurological Surgery, University of Washington;
7 Norcliffe Foundation Center for Integrative Brain Research, Seattle Children’s Research Institute;
8 Division of Rheumatology, University of Washington
Abstract:
Bi-directional maternal-fetal exchange during pregnancy creates long-term persistence of microchimerism (Mc) including in the human brain. However, Mc studies in human brain are limited due to difficulty in obtaining brain tissue concurrent with material for genotyping from related individuals that would allow for identification of microchimerism. To address this gap of knowledge, we obtained surgically resected brain tissue from medication refractory epilepsy patients (aged 28d to 18 years) and buccal swabs from family members. Employing a panel of highly sensitive and specific quantitative PCR assays targeting polymorphisms, mainly in HLA loci, we found a striking prevalence and quantity of maternal-origin Mc (MMc) in resected brain tissue. We next performed single nuclei RNA sequencing (snRNAseq) on tissues from a subset of these patients. We collaborated with colleagues to develop a bioinformatics software for finding rare cells in a disproportionate mixture of two allogeneic entities based on polymorphisms across scRNAseq data to identify Mc. Using this orthogonal method, Mc was identified in pediatric brain and showed strong transcriptional similarity to patient indigenous cells and thus localize alongside patient cells using standard UMAP methodology for clustering of similar cell types. We observed diverse fates acquired by microchimeric cells, including multiple neuronal subtypes, microglia, oligodendrocytes, astrocytes, and endothelial cells. Finally, we applied our methods to publicly available snRNAseq data from individuals with healthy brain development across the lifespan (gestational tissues up to 93 years). Mc was prevalent, detected in most individuals, suggesting persistence in the brain throughout life. Our work provides compelling evidence of the long-term persistence of Mc in human brain, with unprecedented detail into the transcriptional profile and identity of these cells, as provided by novel bioinformatic approaches.