Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement.
Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement.
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DOI：
10.1073/pnas.1717871115
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发表时间：
2018-01-30
影响因子：
11.1
通讯作者：
Greenberg ME
中科院分区：
文献类型：
--
作者：
Kalish BT;Cheadle L;Hrvatin S;Nagy MA;Rivera S;Crow M;Gillis J;Kirchner R;Greenberg ME
随着神经连接的建立，发育中的大脑中的神经元和非神经元细胞动态地调节基因表达。然而，在许多完整的神经元回路的组装和完善过程中，在不同的细胞群中激活的特定基因程序还没有被彻底表征。在这项研究中，我们利用最新进展的转录组分析技术，以表征基因表达在出生后发展的外侧膝状体核（LGN）在单细胞分辨率。我们的数据显示，参与大脑发育的基因在LGN的所有主要细胞类型中受到动态调节，这表明神经连接的建立取决于该大脑区域中多个神经元和非神经元细胞类型之间的功能协作。基因表达的协调变化是中枢神经系统早期模式和细胞类型特化的基础。然而，关于这些变化如何有助于电路组装和改进的后期阶段，人们知之甚少。在这项研究中，我们采用单细胞RNA测序技术，在发育中的背外侧膝状体核（LGN）的四个时间点上开发了一个详细的全转录组基因表达资源，LGN是大脑中的一个视觉结构，它经历了一个很好的表征程序，出生后电路发展。该方法鉴定了定义主要LGN细胞类型的标志物，包括兴奋性中继神经元、少突胶质细胞、星形胶质细胞、小胶质细胞和内皮细胞。大多数细胞类型在发育过程中表现出显著的转录变化，动态表达参与不同过程的基因，包括视网膜定位、突触发生、髓鞘形成和突触细化。我们的数据表明，与突触和电路的发展相关的基因表达在一个更大的比例比以前认识到的非神经元细胞类型。此外，我们使用这个单细胞表达图谱来识别Prkcd-Cre小鼠系作为在感觉驱动的突触细化的后期阶段选择性操纵中继神经元的工具。这种转录组学资源提供了LGN几种细胞类型的基因表达的细胞图谱，并提供了对出生后大脑回路发育的分子机制的见解。
Neurons and nonneuronal cells in the developing brain dynamically regulate gene expression as neural connectivity is established. However, the specific gene programs activated in distinct cell populations during the assembly and refinement of many intact neuronal circuits have not been thoroughly characterized. In this study, we take advantage of recent advances in transcriptomic profiling techniques to characterize gene expression in the postnatal developing lateral geniculate nucleus (LGN) at single-cell resolution. Our data reveal that genes involved in brain development are dynamically regulated in all major cell types of the LGN, suggesting that the establishment of neural connectivity depends upon functional collaboration between multiple neuronal and nonneuronal cell types in this brain region. Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to develop a detailed, whole-transcriptome resource of gene expression across four time points in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in the brain that undergoes a well-characterized program of postnatal circuit development. This approach identifies markers defining the major LGN cell types, including excitatory relay neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells. Most cell types exhibit significant transcriptional changes across development, dynamically expressing genes involved in distinct processes including retinotopic mapping, synaptogenesis, myelination, and synaptic refinement. Our data suggest that genes associated with synapse and circuit development are expressed in a larger proportion of nonneuronal cell types than previously appreciated. Furthermore, we used this single-cell expression atlas to identify the Prkcd-Cre mouse line as a tool for selective manipulation of relay neurons during a late stage of sensory-driven synaptic refinement. This transcriptomic resource provides a cellular map of gene expression across several cell types of the LGN, and offers insight into the molecular mechanisms of circuit development in the postnatal brain.
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影响因子：
4.8
作者：
Bake, Shameena;Okoreeh, Andre K.;Sohrabji, Farida
通讯作者：
Sohrabji, Farida
影响因子：
--
作者：
Dillman AA;Cookson MR
通讯作者：
Cookson MR
影响因子：
8.8
作者：
Fertuzinhos S;Li M;Kawasawa YI;Ivic V;Franjic D;Singh D;Crair M;Sestan N
通讯作者：
Sestan N
影响因子：
6.2
作者：
Anliker, Brigitte;Choi, Ji Woong;Lin, Mu-En;Gardell, Shannon E.;Rivera, Richard R.;Kennedy, Grace;Chun, Jerold
通讯作者：
Chun, Jerold
影响因子：
5.3
作者：
Brockschnieder, D;Sabanay, H;Peles, E
通讯作者：
Peles, E