Single-Cell Analysis Identifies Thymic Maturation Delay in Growth-Restricted Neonatal Mice
Single-Cell Analysis Identifies Thymic Maturation Delay in Growth-Restricted Neonatal Mice
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单细胞分析确定生长受限的新生小鼠胸腺成熟延迟
DOI：
10.1101/372862
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Bacon W
中科院分区：
文献类型：
--
作者：
Bacon W
胎儿生长受限（FGR）会导致新生儿出现各种各样的缺陷，这可能会导致日后患心脏病、糖尿病、焦虑症和其他疾病的风险增加。然而，FGR对免疫系统的影响知之甚少。我们使用了一个特征良好的FGR小鼠模型，其中胎盘特异性Igf-2 P0启动子缺失导致胎盘Igf-2产生丢失。这些动物的胸腺质量减少，细胞减少约70%。我们使用单细胞RNA测序（Drop-Seq）分析了出生后第6天收集的7，264个胸腺细胞。我们发现Cd 8/Cd 4双阳性细胞之间存在相当大的异质性，其中一个亚群显示编码有助于核糖体表面的蛋白质子集的转录本显着上调。来自FGR动物的细胞在该簇中代表性不足。此外，来自FGR动物的细胞的分布是偏斜的，具有较高比例的未成熟双阴性细胞和较少的成熟T细胞。细胞周期调节因子转录本在不同簇之间也存在差异。FGR小鼠的T细胞缺陷持续到成年期，即使由于追赶性生长，体重和器官重量接近正常水平。这一发现补充了在生长受限的人类婴儿中发现的免疫力改变。这种T细胞的减少可能对成人免疫有影响，增加了子宫环境是一个促成因素的成人疾病列表。
Fetal growth restriction (FGR) causes a wide variety of defects in the neonate which can lead to increased risk of heart disease, diabetes, anxiety and other disorders later in life. However, the effect of FGR on the immune system, is poorly understood. We used a well-characterized mouse model of FGR in which placental Igf-2 production is lost due to deletion of the placental specificIgf-2P0promotor. The thymi in such animals were reduced in mass with a ~70% reduction in cellularity. We used single cell RNA sequencing (Drop-Seq) to analyze 7,264 thymus cells collected at postnatal day 6. We identified considerable heterogeneity among the Cd8/Cd4 double positive cells with one subcluster showing marked upregulation of transcripts encoding a sub-set of proteins that contribute to the surface of the ribosome. The cells from the FGR animals were underrepresented in this cluster. Furthermore, the distribution of cells from the FGR animals was skewed with a higher proportion of immature double negative cells and fewer mature T-cells. Cell cycle regulator transcripts also varied across clusters. The T-cell deficit in FGR mice persisted into adulthood, even when body and organ weights approached normal levels due to catch-up growth. This finding complements the altered immunity found in growth restricted human infants. This reduction in T-cellularity may have implications for adult immunity, adding to the list of adult conditions in which thein uteroenvironment is a contributory factor.
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影响因子：
4.4
作者：
Gui, Jingang;Morales, Amanda J.;Craig, Ruth W.
通讯作者：
Craig, Ruth W.
宫内生长受限、内脏血流速度和外分泌胰腺功能
影响因子：
1.8
作者：
R. Nicholl;J. Deenmamode;H. Gamsu
通讯作者：
H. Gamsu
影响因子：
7.1
作者：
Moore, SE;Jalil, F;Hanson, LÅ
通讯作者：
Hanson, LÅ
DOI：
10.1084/jem.20042524
发表时间：
2005-06-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dik WA;Pike-Overzet K;Weerkamp F;de Ridder D;de Haas EF;Baert MR;van der Spek P;Koster EE;Reinders MJ;van Dongen JJ;Langerak AW;Staal FJ
通讯作者：
Staal FJ
人类 T 细胞的单细胞 RNA 测序。
影响因子：
--
作者：
A. Villani;K. Shekhar
通讯作者：
K. Shekhar