Whole-embryonic identification of maternal microchimeric cell types in mouse using single-cell RNA sequencing

Area of Science:

• Reproductive immunology
• Developmental biology
• Cellular and molecular biology

Background:

• Mammalian mothers and fetuses are immunologically distinct, yet exchange cells.
• Maternal microchimeric cells (MMc cells) are found in fetuses and linked to various physiological and pathological outcomes.
• The specific contribution of MMc cell types to fetal development and disease remains unclear.

Purpose of the Study:

• To investigate the hypothesis that differing MMc cell type repertoires in embryos influence developmental outcomes.
• To develop a method for identifying MMc cell types within individual whole embryos.
• To analyze the variability of MMc cell types across different embryos.

Main Methods:

• Isolation of MMc cells from whole mouse embryos.
• Application of single-cell RNA sequencing to determine MMc cell types.
• Analysis of MMc cell type repertoires and their inter-individual variation.

Main Results:

• Successfully estimated MMc cell type repertoires in 26 individual mouse embryos.
• Identified MMc cells as predominantly immune-related (myeloid, granulocytes), with stem cell-like and terminally differentiated types also detected.
• Observed statistically significant inter-individual variation in the proportion of immune-related MMc cells among embryos.

Conclusions:

• The proportion of immune-related MMc cells significantly differs among individual embryos.
• This variation in MMc cell composition is a potential mechanism explaining differing MMc-related physiological phenomena in offspring.
• Findings offer insights into cell-level epigenetics mediated by maternal cells.