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揭示尾蚴幼虫细胞类型、发育途径和组织架构的单细胞图谱。

A single-cell atlas of the miracidium larva of reveals cell types, developmental pathways, and tissue architecture.

机构信息

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom.

School of Infection and Immunity, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.

出版信息

Elife. 2024 Aug 27;13:RP95628. doi: 10.7554/eLife.95628.

Abstract

is a parasitic flatworm that causes the major neglected tropical disease schistosomiasis. The miracidium is the first larval stage of the life cycle. It swims and infects a freshwater snail, transforms into a mother sporocyst, where its stem cells generate daughter sporocysts that give rise to human-infective cercariae larvae. To understand the miracidium at cellular and molecular levels, we created a whole-body atlas of its ~365 cells. Single-cell RNA sequencing identified 19 transcriptionally distinct cell clusters. In situ hybridisation of tissue-specific genes revealed that 93% of the cells in the larva are somatic (57% neural, 19% muscle, 13% epidermal or tegument, 2% parenchyma, and 2% protonephridia) and 7% are stem. Whereas neurons represent the most diverse somatic cell types, trajectory analysis of the two main stem cell populations indicates that one of them is the origin of the tegument lineage and the other likely contains pluripotent cells. Furthermore, unlike the somatic cells, each of these stem populations shows sex-biased transcriptional signatures suggesting a cell-type-specific gene dosage compensation for sex chromosome-linked loci. The miracidium represents a simple developmental stage with which to gain a fundamental understanding of the molecular biology and spatial architecture of schistosome cells.

摘要

是一种寄生扁形动物,它会导致主要的被忽视热带病——血吸虫病。毛蚴是生命周期的第一个幼虫阶段。它在淡水中游泳并感染淡水螺,然后转化为母孢囊,其干细胞在母孢囊中生成可感染人类的尾蚴幼虫。为了在细胞和分子水平上了解毛蚴,我们创建了其约 365 个细胞的全身图谱。单细胞 RNA 测序鉴定出 19 个转录上不同的细胞簇。组织特异性基因的原位杂交显示,幼虫中的 93%的细胞是体细胞(57%是神经细胞,19%是肌肉细胞,13%是表皮或表皮细胞,2%是实质细胞,2%是原肾细胞),7%是干细胞。虽然神经元代表了最具多样性的体细胞类型,但对两个主要干细胞群的轨迹分析表明,其中一个是表皮谱系的起源,另一个可能含有多能细胞。此外,与体细胞不同,这些干细胞群体中的每一个都表现出性别偏倚的转录特征,这表明性染色体连锁基因座存在细胞类型特异性的基因剂量补偿。毛蚴代表了一个简单的发育阶段,可以帮助我们深入了解血吸虫细胞的分子生物学和空间结构。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b8/11349301/17491381c981/elife-95628-fig1.jpg

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