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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单细胞分析确定了生长限制的新生儿小鼠的胸腺成熟延迟。
DOI：
10.3389/fimmu.2018.02523
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发表时间：
2018
影响因子：
7.3
通讯作者：
Charnock-Jones DS
中科院分区：
文献类型：
--
作者：
Bacon WA;Hamilton RS;Yu Z;Kieckbusch J;Hawkes D;Krzak AM;Abell C;Colucci F;Charnock-Jones DS
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。我们确定了相当大的异质性之间的Cd 8/Cd 4双阳性细胞与一个亚群显示显着上调的转录本编码的一个子集的蛋白质，有助于核糖体的表面。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力有影响，增加了子宫内环境是促成因素的成人条件列表。
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 specific Igf-2 P0 promotor. 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 the in utero environment 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.
影响因子：
3.6
作者：
KARLBERG, J;ALBERTSSONWIKLAND, K
通讯作者：
ALBERTSSONWIKLAND, K
单细胞RNA测序揭示了T辅助细胞合成从头开始的类固醇，从而有助于免疫稳态。
影响因子：
8.8
作者：
Mahata B;Zhang X;Kolodziejczyk AA;Proserpio V;Haim-Vilmovsky L;Taylor AE;Hebenstreit D;Dingler FA;Moignard V;Göttgens B;Arlt W;McKenzie AN;Teichmann SA
通讯作者：
Teichmann SA
影响因子：
3.9
作者：
Boria, Ilenia;Garelli, Emanuela;Gazda, Hanna T.;Aspesi, Anna;Quarello, Paola;Pavesi, Elisa;Ferrante, Daniela;Meerpohl, Joerg J.;Kartal, Mutlu;Da Costa, Lydie;Proust, Alexis;Leblanc, Thierry;Simansour, Maud;Dahl, Niklas;Froejmark, Anne-Sophie;Pospisilova, Dagmar;Cmejla, Radek;Beggs, Alan H.;Sheen, Mee R.;Landowski, Michael;Buros, Christopher M.;Clinton, Catherine M.;Dobson, Lori J.;Vlachos, Adrianna;Atsidaftos, Eva;Lipton, Jeffrey M.;Ellis, Steven R.;Ramenghi, Ugo;Dianzani, Irma
通讯作者：
Dianzani, Irma
在脂肪组织中胰岛素耐药的表型后，捕获胰岛素抗性的表型后，追赶生长。
影响因子：
4.9
作者：
Berends, L. M.;Fernandez-Twinn, D. S.;Martin-Gronert, M. S.;Cripps, R. L.;Ozanne, S. E.
通讯作者：
Ozanne, S. E.