Differentiation trajectories of the Hydra nervous system reveal transcriptional regulators of neuronal fate.
Differentiation trajectories of the Hydra nervous system reveal transcriptional regulators of neuronal fate.
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水螅神经系统的分化轨迹揭示了神经元命运的转录调节因子。
DOI：
10.1101/2023.03.15.531610
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Juliano,CelinaE
中科院分区：
文献类型：
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作者：
Primack,AbbyS;Cazet,JackF;Little,HannahMorris;Mühlbauer,Susanne;Cox,BenD;David,CharlesN;Farrell,JeffreyA;Juliano,CelinaE
小型淡水刺胞动物水螅在其一生中使用成体干细胞（间质干细胞）不断替换神经元。该特征与对整个神经系统成像的能力相结合（Badhiwala等人，2021; Dupre & Yuste，2017）和基因敲低技术的可用性（Juliano，赖希，et al.，2014; Lohmann等人，1999; Vogg等人，2022），使Hydra成为研究整个生物体水平神经系统发育和再生的易处理模型。在这项研究中，我们使用单细胞RNA测序和轨迹推断提供了一个全面的成人神经系统的分子描述。这包括迄今为止最详细的成年水螅神经系统的转录特征。我们鉴定了11种独特的神经元亚型，以及间质干细胞分化为每种亚型时发生的转录变化。为了建立基因调控网络来描述水螅神经元分化的目标，我们确定了48个在水螅神经系统中特异性表达的转录因子，其中包括许多在双侧性神经发生中保守的调节因子。我们还对分选的神经元进行了ATAC-seq，以揭示神经元特异性基因附近先前未识别的推定调控区域。最后，我们提供的证据支持成熟的神经元亚型之间的转分化的存在，我们确定以前未知的过渡状态，在这些途径。总之，我们提供了一个全面的转录描述整个成人神经系统，包括分化和转分化途径，这提供了一个重要的进展，了解神经系统再生的机制。
The small freshwater cnidarian polyp Hydra vulgaris uses adult stem cells (interstitial stem cells) to continually replace neurons throughout its life. This feature, combined with the ability to image the entire nervous system (Badhiwala et al., 2021; Dupre & Yuste, 2017) and availability of gene knockdown techniques (Juliano, Reich, et al., 2014; Lohmann et al., 1999; Vogg et al., 2022), makes Hydra a tractable model for studying nervous system development and regeneration at the whole-organism level. In this study, we use single-cell RNA sequencing and trajectory inference to provide a comprehensive molecular description of the adult nervous system. This includes the most detailed transcriptional characterization of the adult Hydra nervous system to date. We identified eleven unique neuron subtypes together with the transcriptional changes that occur as the interstitial stem cells differentiate into each subtype. Towards the goal of building gene regulatory networks to describe Hydra neuron differentiation, we identified 48 transcription factors expressed specifically in the Hydra nervous system, including many that are conserved regulators of neurogenesis in bilaterians. We also performed ATAC-seq on sorted neurons to uncover previously unidentified putative regulatory regions near neuron-specific genes. Finally, we provide evidence to support the existence of transdifferentiation between mature neuron subtypes and we identify previously unknown transition states in these pathways. All together, we provide a comprehensive transcriptional description of an entire adult nervous system, including differentiation and transdifferentiation pathways, which provides a significant advance towards understanding mechanisms that underlie nervous system regeneration.