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.胎儿生长受限（FGR）可引发新生儿出现多种发育缺陷，进而在其日后的生活中增加罹患心脏病、糖尿病、焦虑症及其他病症的风险。然而，目前学界对胎儿生长受限对免疫系统的影响尚知之甚少。在整个发育过程中，免疫细胞的区分通常借助细胞表面标志物来识别发育进程中细微不同的阶段，但这类（表面）蛋白未必会导致细胞活性产生差异，因此仅可作为一种偶然且浅表的细胞分类参考依据。研究团队针对新生小鼠胸腺开展了基于DropSeq的高通量单细胞转录组测序：通过流式细胞术分别筛选野生型对照组以及胎盘特异性胰岛素样生长因子2（Igf2）p0亚型敲低（igf2-p0）模型中的T细胞群。通过本次分析，研究人员在生长受限的小鼠新生个体中发现了偏移的T细胞群，提示其存在发育迟缓现象。该发现印证了生长受限人类婴儿所出现的免疫功能异常。即便通过追赶生长使得体质量与器官重量趋近正常水平，T细胞数量不足的状况仍会持续至成年阶段。这种T细胞丰度的降低可能对成年个体的免疫功能产生重要影响，进一步丰富了目前已知的“成年疾病起源于胎儿期”的多种致病机制。