对源自2型神经母细胞的成年脑神经元进行单核RNA测序,揭示了昆虫中央复合体中的转录复杂性。

Single nuclei RNA-sequencing of adult brain neurons derived from type 2 neuroblasts reveals transcriptional complexity in the insect central complex.

作者信息

Epiney Derek G, Chaya Gonzalo Morales, Dillon Noah R, Lai Sen-Lin, Doe Chris Q

机构信息

Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, United States.

出版信息

Elife. 2025 May 15;14:RP105896. doi: 10.7554/eLife.105896.

Abstract

In both and mammals, the brain contains the most diverse population of cell types of any tissue. It is generally accepted that transcriptional diversity is an early step in generating neuronal and glial diversity, followed by the establishment of a unique gene expression profile that determines morphology, connectivity, and function. In , there are two types of neural stem cells, called Type 1 (T1) and Type 2 (T2) neuroblasts. The diversity of T2-derived neurons contributes a large portion of the central complex (CX), a conserved brain region that plays a role in sensorimotor integration. Recent work has revealed much of the connectome of the CX, but how this connectome is assembled remains unclear. Mapping the transcriptional diversity of T2-derived neurons is a necessary step in linking transcriptional profile to the assembly of the adult brain. Here we perform single nuclei RNA sequencing of T2 neuroblast-derived adult neurons and glia. We identify clusters containing all known classes of glia, clusters that are male/female enriched, and 161 neuron-specific clusters. We map neurotransmitter and neuropeptide expression and identify unique transcription factor combinatorial codes for each cluster. This is a necessary step that directs functional studies to determine whether each transcription factor combinatorial code specifies a distinct neuron type within the CX. We map several columnar neuron subtypes to distinct clusters and identify two neuronal classes (NPF+ and AstA+) that both map to two closely related clusters. Our data support the hypothesis that each transcriptional cluster represents one or a few closely related neuron subtypes.

摘要

在果蝇和哺乳动物中,大脑包含所有组织中细胞类型最多样化的群体。人们普遍认为,转录多样性是产生神经元和神经胶质多样性的早期步骤,随后建立独特的基因表达谱,该谱决定形态、连接性和功能。在果蝇中,有两种类型的神经干细胞,称为1型(T1)和2型(T2)神经母细胞。T2衍生神经元的多样性构成了中央复合体(CX)的很大一部分,CX是一个保守的脑区,在感觉运动整合中起作用。最近的研究揭示了CX的许多连接组,但这种连接组是如何组装的仍不清楚。绘制T2衍生神经元的转录多样性图谱是将转录谱与成体大脑组装联系起来的必要步骤。在这里,我们对T2神经母细胞衍生的成体神经元和神经胶质进行单核RNA测序。我们确定了包含所有已知神经胶质类别的簇、富含雄性/雌性的簇以及161个神经元特异性簇。我们绘制了神经递质和神经肽的表达图谱,并确定了每个簇独特的转录因子组合代码。这是指导功能研究以确定每个转录因子组合代码是否在CX内指定不同神经元类型的必要步骤。我们将几种柱状神经元亚型映射到不同的簇,并确定了两个神经元类别(NPF+和AstA+),它们都映射到两个密切相关的簇。我们的数据支持这样的假设,即每个转录簇代表一种或几种密切相关的神经元亚型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70dd/12081001/92bb3c8659a0/elife-105896-fig1.jpg

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