Neuronal identities derived by misexpression of the POU IV sensory determinant in a protovertebrate.
Neuronal identities derived by misexpression of the POU IV sensory determinant in a protovertebrate.
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DOI：
10.1073/pnas.2118817119
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发表时间：
2022-01-25
影响因子：
11.1
通讯作者：
Levine M
中科院分区：
文献类型：
--
作者：
Chacha PP;Horie R;Kusakabe TG;Sasakura Y;Singh M;Horie T;Levine M
原索动物玻璃海鞘（Ciona intestinalis）是一个理想的系统，可用于研究构成细胞类型特化基础的基因调控网络以及细胞类型是如何进化的。在这项研究中，我们利用单细胞技术、实验操作和计算分析来了解调控决定因子POU IV（脊椎动物中Brn3的同源物）在玻璃海鞘中特化各种感觉细胞类型的作用。令人惊讶的是，POU IV在整个表皮中的错误表达导致了混合感觉细胞类型的形成，包括那些同时表现出触须感觉细胞和双极尾神经元特性的细胞。这些结果证明了不同感觉特化网络之间的相互联系，并为通过靶向错误表达细胞决定因子对细胞类型进行重编程的机遇和挑战提供了见解。
原索动物玻璃海鞘A型（有时称为强壮玻璃海鞘，Ciona robusta）包含一系列分布在游泳蝌蚪头尾轴上的感觉细胞类型。它们源自神经板的侧部区域，这些区域表现出脊椎动物基板和神经嵴的特性。已知感觉决定因子POU IV/Brn3与区域决定因子（如Foxg和Neurogenin）协同作用，分别在头部和尾部区域产生触须感觉细胞（PSCs）和双极尾神经元（BTNs）。单细胞RNA测序（scRNA - seq）分析、计算分析和实验操作相结合的结果表明，POU IV的错误表达导致表皮细胞可变地转化为混合感觉细胞类型，包括那些同时表现出PSCs和BTNs特性的细胞。混合特性是由于由一个意想不到的POU IV反馈回路触发的Foxg和Neurogenin的共表达。还发现混合细胞表达一种在任何已知细胞类型中都不共表达的合成基因簇。我们根据通过靶向错误表达细胞决定因子对细胞类型进行重编程的机遇和挑战来讨论这些结果。
The protovertebrate Ciona intestinalis is an ideal system to investigate both gene regulatory networks that underlie cell-type specification and how cell types have evolved. In this study, we use single-cell technology, experimental manipulations, and computational analyses to understand the role of the regulatory determinant POU IV—a homolog of Brn3 in vertebrates—in specifying various sensory cell types in Ciona. Surprisingly, the misexpression of POU IV throughout the epidermis led to the formation of hybrid sensory cell types, including those exhibiting properties of both palp sensory cells and bipolar tail neurons. These results demonstrate the interconnectedness of diverse sensory specification networks and give insights into the opportunities and challenges of reprogramming cell types through the targeted misexpression of cellular determinants. The protovertebrate Ciona intestinalis type A (sometimes called Ciona robusta) contains a series of sensory cell types distributed across the head–tail axis of swimming tadpoles. They arise from lateral regions of the neural plate that exhibit properties of vertebrate placodes and neural crest. The sensory determinant POU IV/Brn3 is known to work in concert with regional determinants, such as Foxg and Neurogenin, to produce palp sensory cells (PSCs) and bipolar tail neurons (BTNs), in head and tail regions, respectively. A combination of single-cell RNA-sequencing (scRNA-seq) assays, computational analysis, and experimental manipulations suggests that misexpression of POU IV results in variable transformations of epidermal cells into hybrid sensory cell types, including those exhibiting properties of both PSCs and BTNs. Hybrid properties are due to coexpression of Foxg and Neurogenin that is triggered by an unexpected POU IV feedback loop. Hybrid cells were also found to express a synthetic gene battery that is not coexpressed in any known cell type. We discuss these results with respect to the opportunities and challenges of reprogramming cell types through the targeted misexpression of cellular determinants.
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