Single-cell RNA transcriptome reveals embryonic origin of offspring fibrosis due to maternal obesity

Over 40% of pregnant American women are obese which negatively affects fetal development with long-term consequences for offspring health. Maternal obesity (MO) leads to fibrotic infiltration in skeletal muscle, brown adipose tissue, and other tissues/organs of offspring, but mechanisms remain to be defined. Using a mouse model of diet-induced obesity and unbiased single-cell RNA-sequencing (scRNA-seq), we tested the effeCONs of MO on embryonic fibrogenesis, which serves as the source of fibrogenic and stromal cells in adults. Embryonic somatic tissues were obtained at E9.5, E11.5 and E13.5 of control (CON) and MO mice. Using unsupervised clustering of scRNA-seq data, we identified three major cell clusters with increasing fibrogenic capacity. Compared to CON, the population of fibrogenic cells increased dramatically due to MO, correlated with the elevated expression of transforming growth factor ß (Tgfb) and paired related homeobox 1 (Prrx1), as well as fibrogenic genes. Overall design: Single-cell transcriptomic profiling of mouse embryos on embryonic 9.5, 11.5 and 13.5 day from maternal lean or obese mothers.