Insulin-like growth factor 2 (IGF2) as a driving force of exponential expansion and differentiation of neonatal thymus.

IF 3.7 2区生物学 Q1 DEVELOPMENTAL BIOLOGY

Development Pub Date : 2025-03-20 DOI:10.1242/dev.204347

Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Anusha Vasudev, Ken S Lau, Qi Liu, Ellen R Richie, Laura P Hale, Nancy R Manley

{"title":"Insulin-like growth factor 2 (IGF2) as a driving force of exponential expansion and differentiation of neonatal thymus.","authors":"Seung Woo Kang, Bryan R Helm, Yu Wang, Shiyun Xiao, Wen Zhang, Anusha Vasudev, Ken S Lau, Qi Liu, Ellen R Richie, Laura P Hale, Nancy R Manley","doi":"10.1242/dev.204347","DOIUrl":null,"url":null,"abstract":"<p><p>Like all organs, the thymus grows in size and function rapidly during development, which comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated IGF2 activity promotes a cortical TEC-specific proliferation and is tightly regulated at the thymic growth transition. Bulk RNA-seq of human thymi across the transition also revealed IGF2 to drive thymic expansion, suggesting an evolutionarily conserved role. Our study highlights the role of a fibroblast-derived IGF2 in promoting cTEC proliferation and differentiation, resulting in early thymic expansion that is followed by down-regulation to establish homeostasis.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Development","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1242/dev.204347","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Like all organs, the thymus grows in size and function rapidly during development, which comes to a halt after birth. However, the molecular mechanisms behind such a transition in the thymus remain obscure. Using single-cell RNA sequencing (scRNA-seq) of the murine thymic stroma, we identified that major transcriptomic changes occur in the endothelium and mesenchyme across the transition to homeostasis. Differentially expressed gene and intercellular network analyses of temporally resolved scRNA-seq data revealed fibroblast-derived insulin-like growth factor 2 (IGF2) as a candidate driving neonatal thymic expansion. We demonstrated IGF2 activity promotes a cortical TEC-specific proliferation and is tightly regulated at the thymic growth transition. Bulk RNA-seq of human thymi across the transition also revealed IGF2 to drive thymic expansion, suggesting an evolutionarily conserved role. Our study highlights the role of a fibroblast-derived IGF2 in promoting cTEC proliferation and differentiation, resulting in early thymic expansion that is followed by down-regulation to establish homeostasis.

查看原文本刊更多论文

胰岛素样生长因子2 （IGF2）作为新生儿胸腺指数扩张和分化的驱动力。

像所有器官一样，胸腺在发育过程中大小和功能迅速增长，出生后就停止了。然而，在胸腺中这种转变背后的分子机制仍然不清楚。利用小鼠胸腺基质的单细胞RNA测序（scRNA-seq），我们发现内皮和间质在向稳态过渡的过程中发生了主要的转录组变化。对临时解析的scRNA-seq数据的差异表达基因和细胞间网络分析显示，成纤维细胞衍生的胰岛素样生长因子2 （IGF2）是驱动新生儿胸腺扩张的候选因子。我们证明了IGF2活性促进皮质tec特异性增殖，并在胸腺生长转变中受到严格调节。人类胸腺的大量rna测序也揭示了IGF2驱动胸腺扩张，表明其在进化上的保守作用。我们的研究强调了成纤维细胞衍生的IGF2在促进cTEC增殖和分化中的作用，导致早期胸腺扩张，随后下调以建立稳态。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Development 生物-发育生物学

CiteScore

6.70

自引率

4.30%

发文量

433

审稿时长

3 months

期刊介绍： Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.