Spatial Gene-Expression Gradients Underlie Prominent Heterogeneity of CA1 Pyramidal Neurons
Spatial Gene-Expression Gradients Underlie Prominent Heterogeneity of CA1 Pyramidal Neurons
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DOI：
10.1016/j.neuron.2015.12.013
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发表时间：
2016-01-20
期刊：
影响因子：
16.2
通讯作者：
Spruston, Nelson
中科院分区：
文献类型：
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作者：
Cembrowski, Mark S.;Bachman, Julia L.;Spruston, Nelson
组织和器官功能通常被理解为离散和同质细胞类型之间的相互作用。这种方法在神经科学中已经被证明是困难的，因为不同神经元类别之间存在显著的多样性，但它可能会受到显著的类内变异性的进一步阻碍。在这里，我们认为一个定义明确的典型的神经元群体海马CA1锥体细胞（CA1 PC）和系统地研究转录异质性的程度和空间规则。使用下一代RNA测序，我们确定了CA1 PC的显著变异性，使得CA1内沿着背腹轴的差异与不同锥体神经元类别之间的差异相媲美。这种变异性来自于一系列连续的基因表达梯度，产生了与多种多样的细胞连续体相一致的转录谱。这项工作揭示了一个典型的和狭义的神经元群体内的变异性意想不到的量，并表明，连续的，类内异质性可能是神经回路的一个重要特征。
Tissue and organ function has been conventionally understood in terms of the interactions among discrete and homogeneous cell types. This approach has proven difficult in neuroscience due to the marked diversity across different neuron classes, but it may be further hampered by prominent within-class variability. Here, we considered a well-defined canonical neuronal population-hippocampal CA1 pyramidal cells (CA1 PCs)-and systematically examined the extent and spatial rules of transcriptional heterogeneity. Using next-generation RNA sequencing, we identified striking variability in CA1 PCs, such that the differences within CA1 along the dorsal-ventral axis rivaled differences across distinct pyramidal neuron classes. This variability emerged from a spectrum of continuous geneexpression gradients, producing a transcriptional profile consistent with a multifarious continuum of cells. This work reveals an unexpected amount of variability within a canonical and narrowly defined neuronal population and suggests that continuous, within-class heterogeneity may be an important feature of neural circuits.