Comparative single-cell transcriptional atlases of Babesia species reveal conserved and species-specific expression profiles.

Comparative single-cell transcriptional atlases of Babesia species reveal conserved and species-specific expression profiles.
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DOI:
10.1371/journal.pbio.3001816
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发表时间:
2022-09
期刊:
影响因子:
9.8
通讯作者:
--
中科院分区:
生物学1区
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巴贝虫是一种顶复门寄生虫,感染脊椎动物宿主的红细胞。病理发生在无性血液感染阶段的快速复制周期期间。目前对巴氏疟原虫复制周期进展和调控的了解有限,主要依赖于与相关寄生虫的比较研究。由于在同步Bababelus寄生虫的限制,精细尺度的时间过程转录组学资源是不容易获得的。单细胞转录组学为分析异步细胞群提供了一个强大的无偏替代方案。在此,我们将单细胞RNA测序应用于3种Babelae物种(B. divergens,B.牛和B. bigemina)。我们使用分析方法和算法来绘制复制周期并构建伪同步的时间过程基因表达谱。我们确定集群的共表达基因显示“即时”的表达谱,在整个无性发育逐渐级联峰。此外,聚类分析重建的基因曲线揭示了协调的时间表观遗传标记和转录因子的峰值表达。使用正则化高斯图形模型,我们重建了共表达网络,并确定了保守和物种特异性节点。AP2转录因子的共表达相互作用组的基序分析确定了先前报道的在疟原虫属物种的DNA复制中发挥作用的特定基序。最后,我们提出了一个交互式的Web应用程序来可视化和交互式地探索数据集。巴氏疟原虫是一种感染脊椎动物红细胞的顶复门寄生虫属,但同步寄生虫的困难限制了巴氏疟原虫复制周期的知识。本研究利用单细胞RNA测序的三个Babelands物种的复制周期和构建伪同步的时间过程基因表达谱。
Babesia is a genus of apicomplexan parasites that infect red blood cells in vertebrate hosts. Pathology occurs during rapid replication cycles in the asexual blood stage of infection. Current knowledge of Babesia replication cycle progression and regulation is limited and relies mostly on comparative studies with related parasites. Due to limitations in synchronizing Babesia parasites, fine-scale time-course transcriptomic resources are not readily available. Single-cell transcriptomics provides a powerful unbiased alternative for profiling asynchronous cell populations. Here, we applied single-cell RNA sequencing to 3 Babesia species (B. divergens, B. bovis, and B. bigemina). We used analytical approaches and algorithms to map the replication cycle and construct pseudo-synchronized time-course gene expression profiles. We identify clusters of co-expressed genes showing “just-in-time” expression profiles, with gradually cascading peaks throughout asexual development. Moreover, clustering analysis of reconstructed gene curves reveals coordinated timing of peak expression in epigenetic markers and transcription factors. Using a regularized Gaussian graphical model, we reconstructed co-expression networks and identified conserved and species-specific nodes. Motif analysis of a co-expression interactome of AP2 transcription factors identified specific motifs previously reported to play a role in DNA replication in Plasmodium species. Finally, we present an interactive web application to visualize and interactively explore the datasets. Babesia is a genus of apicomplexan parasites that infect vertebrate red blood cells, but difficulties in synchronizing the parasites has limited knowledge of the Babesia replication cycle. This study uses single-cell RNA sequencing of three Babesia species to map the replication cycle and construct pseudo-synchronized time-course gene expression profiles.
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影响因子: 3.7
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