E-MTAB-6945
Single-cell analysis of T-cells from mouse neonate thymuses in a wild type control and a placental specific isoform of Igf2 knock-down (igf2-P0)
Fetal growth restriction (FGR) causes a wide variety of developmental defects in the neonate which can lead to heart disease, diabetes, anxiety and other disorders later in life. The effect of FGR on the immune system, however, is poorly understood. Immune cells throughout development are identified using cell-surface markers to distinguish between subtly different stages. These (surface) proteins, however, do not necessarily generate differences in cellular activity and may thus be only a coincidental shallow guide to classifying cells. High-throughput single-cell transcriptomics using DropSeq was performed on mouse neonate thymuses. The T-cell population was selected through flow cytometry in wild type controls and a placental specific isoform of Igf2 knock-down (igf2-p0). Using this analysis, we discovered skewed T-cell populations in the growth restricted murine neonate indicating a developmental delay. This finding recapitulates the altered immunity found in growth restricted human infants. The T-cell deficit persisted into adulthood, even when body and organ weights approached normal levels due to catch-up growth. This reduction in T-cellularity may have significant implications in adult immunity, adding to the wide variety of fetal origins for adult disease already known.
Fetal growth restriction (FGR) causes a wide variety of developmental defects in the neonate which can lead to heart disease, diabetes, anxiety and other disorders later in life. The effect of FGR on the immune system, however, is poorly understood. Immune cells throughout development are identified using cell-surface markers to distinguish between subtly different stages. These (surface) proteins, however, do not necessarily generate differences in cellular activity and may thus be only a coincidental shallow guide to classifying cells. High-throughput single-cell transcriptomics using DropSeq was performed on mouse neonate thymuses. The T-cell population was selected through flow cytometry in wild type controls and a placental specific isoform of Igf2 knock-down (igf2-p0). Using this analysis, we discovered skewed T-cell populations in the growth restricted murine neonate indicating a developmental delay. This finding recapitulates the altered immunity found in growth restricted human infants. The T-cell deficit persisted into adulthood, even when body and organ weights approached normal levels due to catch-up growth. This reduction in T-cellularity may have significant implications in adult immunity, adding to the wide variety of fetal origins for adult disease already known.