Elucidating the Role of Migratory Fetal Cells Found in the Lungs of Pregnant Woman

ABSTRACT Rationale and Goal: During pregnancy, fetal cells (FCs) have been known to enter the maternal circulation where they can then migrate to various maternal organs, interacting with the maternal microenvironment. What remains unclear, however, is the cellular identity and molecular characteristics of these migratory fetal cells. The goal of my research is to identify and characterize the migratory FCs that home to the maternal lung, and explore their angiogenic activities and potential to mediate organ repair by adapting an endothelial cell-like phenotype. Methods and Results: To identify and characterize these putative regenerative FCs, I set up timed breeding experiments using a RosamT/mG+ male reporter mouse and crossed it with wild-type (WT) C57BL6 female mouse. After timed matings, vascularized organs were harvested late gestation, and stained sections subjected to high-resolution epifluorescence microscopy examining for co-localization between RFP+ fetal cells and endothelial-specific markers CD31 and VE-Cadherin. In order to confirm the presence of FC gene and endothelial lineage markers, we performed PCR by using FC-specific PCR primers to amplify gene products, prepared from the maternal vascular tissues. PCR confirmed the presence of FC gene in the pregnant mothers’ lung tissue. Furthermore, live microscopy analysis of thin cryosections showed the presence of FCs in the pregnant mouse vascular tissues, while control virgin female mice did not. After completing whole transcriptome sequencing, we have additionally identified several lncRNA transcriptional targets that may contribute to the notable increase in Flk1 expression within the maternal lung during Pregnancy. Summary: Our results indicate the presence of RosamT/mG+ FCs in maternal tissues. Importantly, a subset of these FCs incorporated into CD31+ vascular structures. Additionally, I have identified a subset of candidate lncRNA in maternal lung tissue which are likely to be expressed as an adaptive response.