Single-cell RNA sequencing of Plasmodium vivax sporozoites reveals stage- and species-specific transcriptomic signatures.
Single-cell RNA sequencing of Plasmodium vivax sporozoites reveals stage- and species-specific transcriptomic signatures.
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DOI：
10.1371/journal.pntd.0010633
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发表时间：
2022-08
影响因子：
3.8
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间日疟原虫子孢子在感染人类宿主并引起疟疾之前存在于蚊子的唾液腺中。以前在这些寄生虫形式的群体中进行的全转录组研究在阐明细胞间变异的能力方面受到限制，从而掩盖了在理解疟疾传播结果方面可能重要的细胞状态。在这项研究中，我们对9,947个间日疟原虫子孢子进行了转录谱分析，以评估它们在单细胞分辨率上的差异程度。我们发现，子孢子居住在蚊子的唾液腺中存在于不同的发展状态，所定义的转录组签名。此外，相对于恶性疟原虫，间日疟原虫显示出重叠和独特的基因使用模式，突出了保守和物种特异性的基因程序。值得注意的是，将间日疟原虫与恶性疟原虫区分开来是间日疟原虫子孢子表达与翻译调控和抑制相关的基因的子集。最后，我们比较了间日疟原虫子孢子和红细胞形式的单细胞转录组数据，揭示了子孢子特有的基因使用模式。在定义单个间日疟原虫子孢子的转录组特征时，我们的工作为驱动其发育轨迹的因素提供了新的见解，并为更全面的间日疟原虫细胞图谱奠定了基础。间日疟原虫是全球第二大常见的疟疾病因。消除疟疾尤其具有挑战性，因为它既形成活动性血液阶段感染，也形成可持续较长时间的无症状肝脏阶段感染。肝脏中持续存在形式（催眠虫）的激活是蚊子叮咬初次感染后数周或数月复发感染的原因。间日疟原虫如何在肝脏中持续存在仍然是对这种生物体理解的一个主要空白。据推测，当感染性子孢子在唾液腺中时，存在感染性子孢子的预编程，其决定细胞一旦在肝脏中的命运是朝向立即肝脏阶段发育进展还是作为催眠子长期存在。本研究的目的是，看看这种差异是在唾液腺子孢子的转录水平区分。虽然我们发现子孢子之间的显着变化，我们没有发现明确的证据表明，他们是转录预编程的建议。然而，我们强调了几个有趣的模式，似乎是间日疟原虫特异性相对于非复发性物种，导致疟疾，促使进一步调查。
Plasmodium vivax sporozoites reside in the salivary glands of a mosquito before infecting a human host and causing malaria. Previous transcriptome-wide studies in populations of these parasite forms were limited in their ability to elucidate cell-to-cell variation, thereby masking cellular states potentially important in understanding malaria transmission outcomes. In this study, we performed transcription profiling on 9,947 P. vivax sporozoites to assess the extent to which they differ at single-cell resolution. We show that sporozoites residing in the mosquito’s salivary glands exist in distinct developmental states, as defined by their transcriptomic signatures. Additionally, relative to P. falciparum, P. vivax displays overlapping and unique gene usage patterns, highlighting conserved and species-specific gene programs. Notably, distinguishing P. vivax from P. falciparum were a subset of P. vivax sporozoites expressing genes associated with translational regulation and repression. Finally, our comparison of single-cell transcriptomic data from P. vivax sporozoite and erythrocytic forms reveals gene usage patterns unique to sporozoites. In defining the transcriptomic signatures of individual P. vivax sporozoites, our work provides new insights into the factors driving their developmental trajectory and lays the groundwork for a more comprehensive P. vivax cell atlas. Plasmodium vivax is the second most common cause of malaria worldwide. It is particularly challenging for malaria elimination as it forms both active blood-stage infections, as well as asymptomatic liver-stage infections that can persist for extended periods of time. The activation of persister forms in the liver (hypnozoites) are responsible for relapsing infections occurring weeks or months following primary infection via a mosquito bite. How P. vivax persists in the liver remains a major gap in understanding of this organism. It has been hypothesized that there is pre-programming of the infectious sporozoite while it is in the salivary-glands that determines if the cell’s fate once in the liver is to progress towards immediate liver stage development or persist for long-periods as a hypnozoite. The aim of this study was to see if such differences were distinguishable at the transcript level in salivary-gland sporozoites. While we found significant variation amongst sporozoites, we did not find clear evidence that they are transcriptionally pre-programmed as has been suggested. Nevertheless, we highlight several intriguing patterns that appear to be P. vivax specific relative to non-relapsing species that cause malaria prompting further investigation.