Academic Journal
Single-Cell Analysis Identifies Thymic Maturation Delay in Growth-Restricted Neonatal Mice
| العنوان: | Single-Cell Analysis Identifies Thymic Maturation Delay in Growth-Restricted Neonatal Mice |
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| المؤلفون: | Bacon, Wendi, Hamilton, Russell, Yu, Ziyi, Kieckbusch, Jens, Hawkes, Delia, Krzak, Ada, Abell, Chris, Colucci, Francesco, Charnock-Jones, Stephen |
| بيانات النشر: | Frontiers Media //doi.org/10.1101/372862 Frontiers in Immunology |
| سنة النشر: | 2018 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Drop-Seq, T-cell, developmental programming, fetal growth restriction, single-cell, thymus, Animals, Newborn, Disease Models, Animal, Female, Fetal Growth Retardation, Insulin-Like Growth Factor II, Male, Mice, Inbred C57BL, Organ Size, Placenta, Pregnancy, Single-Cell Analysis, Thymus Gland |
| الوصف: | 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 7264 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. ; WB and RH are supported by the Centre for Trophoblast Research. WB, RH, ZY, CA and DC are supported by BBSRC award BB/R008590/1. JK was supported by the RoseTrees Trust, A1525 and the Centre for Trophoblast Research Next Generation Fellowship. FC is supported by the Wellcome Trust Investigator Award 200841/Z/16/Z. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document; video/mpeg; application/octet-stream |
| اللغة: | English |
| Relation: | https://www.repository.cam.ac.uk/handle/1810/285838 |
| DOI: | 10.17863/CAM.33182 |
| الاتاحة: | https://www.repository.cam.ac.uk/handle/1810/285838 https://doi.org/10.17863/CAM.33182 |
| Rights: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.3C2E5B76 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.33182 |
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