{"title":"Systematic single-cell analysis reveals dynamic control of transposable element activity orchestrating the endothelial-to-hematopoietic transition.","authors":"Cong Feng, Ruxiu Tie, Saige Xin, Yuhao Chen, Sida Li, Yifan Chen, Xiaotian Hu, Yincong Zhou, Yongjing Liu, Yueming Hu, Yanshi Hu, Hang Pan, Zexu Wu, Haoyu Chao, Shilong Zhang, Qingyang Ni, Jinyan Huang, Wenda Luo, He Huang, Ming Chen","doi":"10.1186/s12915-024-01939-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse.</p><p><strong>Results: </strong>We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes.</p><p><strong>Conclusions: </strong>Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209969/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12915-024-01939-5","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The endothelial-to-hematopoietic transition (EHT) process during definitive hematopoiesis is highly conserved in vertebrates. Stage-specific expression of transposable elements (TEs) has been detected during zebrafish EHT and may promote hematopoietic stem cell (HSC) formation by activating inflammatory signaling. However, little is known about how TEs contribute to the EHT process in human and mouse.
Results: We reconstructed the single-cell EHT trajectories of human and mouse and resolved the dynamic expression patterns of TEs during EHT. Most TEs presented a transient co-upregulation pattern along the conserved EHT trajectories, coinciding with the temporal relaxation of epigenetic silencing systems. TE products can be sensed by multiple pattern recognition receptors, triggering inflammatory signaling to facilitate HSC emergence. Interestingly, we observed that hypoxia-related signals were enriched in cells with higher TE expression. Furthermore, we constructed the hematopoietic cis-regulatory network of accessible TEs and identified potential TE-derived enhancers that may boost the expression of specific EHT marker genes.
Conclusions: Our study provides a systematic vision of how TEs are dynamically controlled to promote the hematopoietic fate decisions through transcriptional and cis-regulatory networks, and pre-train the immunity of nascent HSCs.
背景:确定性造血过程中的内皮到造血转变(EHT)过程在脊椎动物中高度保守。在斑马鱼EHT过程中已检测到转座元件(TEs)的阶段特异性表达,并可能通过激活炎症信号促进造血干细胞(HSC)的形成。然而,人们对转座元件如何促进人类和小鼠的EHT过程知之甚少:结果:我们重建了人和小鼠的单细胞EHT轨迹,并解析了TEs在EHT过程中的动态表达模式。大多数TE沿着保守的EHT轨迹呈现瞬时共调模式,与表观遗传沉默系统的时间松弛相吻合。TE产物可被多种模式识别受体感知,从而触发炎症信号,促进造血干细胞的出现。有趣的是,我们观察到缺氧相关信号在 TE 表达较高的细胞中富集。此外,我们还构建了可访问TE的造血顺式调控网络,并确定了可能促进特定EHT标记基因表达的潜在TE衍生增强子:我们的研究为我们提供了一个系统的视角,让我们了解 TEs 是如何通过转录和顺式调控网络被动态控制以促进造血命运的决定,并对新生造血干细胞的免疫力进行预训练的。
期刊介绍:
BMC Biology is a broad scope journal covering all areas of biology. Our content includes research articles, new methods and tools. BMC Biology also publishes reviews, Q&A, and commentaries.