@article {65273, title = {Comprehensive transcriptome analysis of cochlear spiral ganglion neurons at multiple ages.}, journal = {eLife}, volume = {9}, year = {2020}, month = {2020 Jan 08}, abstract = {

Inner ear cochlear spiral ganglion neurons (SGNs) transmit auditory information to the brainstem. Recent single cell RNA-Seq studies have revealed heterogeneities within SGNs. Nonetheless, much remains unknown about the transcriptome of SGNs, especially which genes are specifically expressed in SGNs. To address these questions we needed a deeper and broader gene coverage than that in previous studies. We performed bulk RNA-Seq on mouse SGNs at five ages, and on two reference cell types (hair cells and glia). Their transcriptome comparison identified genes previously unknown to be specifically expressed in SGNs. To validate our dataset and provide useful genetic tools for this research field, we generated two knockin mouse strains: and . Our comprehensive analysis confirmed the SGN-selective expression of the candidate genes, testifying to the quality of our transcriptome data. These two mouse strains can be used to temporally label SGNs or to sort them.

}, issn = {2050-084X}, doi = {10.7554/eLife.50491}, author = {Li, Chao and Li, Xiang and Bi, Zhenghong and Sugino, Ken and Wang, Guangqin and Zhu, Tong and Liu, Zhiyong} } @article {48435, title = {Stem cell-intrinsic, seven-up-triggered temporal factor gradients diversify intermediate neural progenitors.}, journal = {Current Biology : CB}, volume = {27}, year = {2017}, month = {2017 Apr 10}, pages = {1303-13}, abstract = {

Building a sizable, complex brain requires both cellular expansion and diversification. One mechanism to achieve these goals is production of multiple transiently amplifying intermediate neural progenitors (INPs) from a single neural stem cell. Like mammalian neural stem cells, Drosophila type II neuroblasts utilize INPs to produce neurons and glia. Within a given lineage, the consecutively born INPs produce morphologically distinct progeny, presumably due to differential inheritance of temporal factors. To uncover the underlying temporal fating mechanisms, we profiled type II neuroblasts{\textquoteright} transcriptome across time. Our results reveal opposing temporal gradients of Imp and Syp RNA-binding proteins (descending and ascending, respectively). Maintaining high Imp throughout serial INP production expands the number of neurons and glia with early temporal fate at the expense of cells with late fate. Conversely, precocious upregulation of Syp reduces the number of cells with early fate. Furthermore, we reveal that the transcription factor Seven-up initiates progression of the Imp/Syp gradients. Interestingly, neuroblasts that maintain initial Imp/Syp levels can still yield progeny with a small range of early fates. We therefore propose that the Seven-up-initiated Imp/Syp gradients create coarse temporal windows within type II neuroblasts to pattern INPs, which subsequently undergo fine-tuned subtemporal patterning.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2017.03.047}, author = {Ren, Qingzhong and Yang, Ching-Po and Liu, Zhiyong and Sugino, Ken and Mok, Kent and He, Yisheng and Ito, Masayoshi and Nern, Aljoscha and Otsuna, Hideo and Lee, Tzumin} } @article {47849, title = {Cell class-lineage analysis reveals sexually dimorphic lineage compositions in the Drosophila brain.}, journal = {Current Biology : CB}, volume = {26}, year = {2016}, month = {2016 Sep 08}, pages = {2583-93}, abstract = {

The morphology and physiology of neurons are directed by developmental decisions made within their lines of descent from single stem cells. Distinct stem cells may produce neurons having shared properties that define their cell class, such as the type of secreted neurotransmitter. The relationship between cell class and lineage is complex. Here we developed the transgenic cell class-lineage intersection (CLIn) system to assign cells of a particular class to specific lineages within the Drosophila brain. CLIn also enables birth-order analysis and genetic manipulation of particular cell classes arising from particular lineages. We demonstrated the power of CLIn in the context of the eight central brain type II lineages, which produce highly diverse progeny through intermediate neural progenitors. We mapped 18 dopaminergic neurons from three distinct clusters to six type\ II lineages that show lineage-characteristic neurite trajectories. In addition, morphologically distinct dopaminergic neurons are produced within a given lineage, and they arise in an invariant sequence. We also identified type II lineages that produce doublesex- and fruitless-expressing neurons and examined whether female-specific apoptosis in these lineages accounts for the lower number of these neurons in the female brain. Blocking apoptosis in these lineages resulted in more cells in both sexes with males still carrying more cells than females. This argues that sex-specific stem cell fate together with differential progeny apoptosis contribute to the final sexual dimorphism.

}, issn = {1879-0445}, doi = {10.1016/j.cub.2016.07.086}, author = {Ren, Qingzhong and Awasaki, Takeshi and Huang, Yu-Fen and Liu, Zhiyong and Lee, Tzumin} } @article {48135, title = {Live cell single molecule-guided Bayesian localization super resolution microscopy.}, journal = {Cell Research}, year = {2016}, month = {2016 Dec 30}, issn = {1748-7838}, doi = {10.1038/cr.2015.160}, author = {Xu, Fan and Zhang, Mingshu and He, Wenting and Han, Renmin and Xue, Fudong and Liu, Zhiyong and Zhang, Fa and Lippincott-Schwartz, Jennifer and Xu, Pingyong} } @article {47307, title = {Transcriptomes of lineage-specific Drosophila neuroblasts profiled by genetic targeting and robotic sorting.}, journal = {Development (Cambridge, England)}, volume = {143}, year = {2016}, month = {2016 Feb 1}, pages = {411-21}, abstract = {

A brain consists of numerous distinct neurons arising from a limited number of progenitors, called neuroblasts in Drosophila. Each neuroblast produces a specific neuronal lineage. To unravel the transcriptional networks that underlie the development of distinct neuroblast lineages, we marked and isolated lineage-specific neuroblasts for RNA sequencing. We labeled particular neuroblasts throughout neurogenesis by activating a conditional neuroblast driver in specific lineages using various intersection strategies. The targeted neuroblasts were efficiently recovered using a custom-built device for robotic single-cell picking. Transcriptome analysis of mushroom body, antennal lobe and type II neuroblasts compared with non-selective neuroblasts, neurons and glia revealed a rich repertoire of transcription factors expressed among neuroblasts in diverse patterns. Besides transcription factors that are likely to be pan-neuroblast, many transcription factors exist that are selectively enriched or repressed in certain neuroblasts. The unique combinations of transcription factors present in different neuroblasts may govern the diverse lineage-specific neuron fates.

}, issn = {1477-9129}, doi = {10.1242/dev.129163}, author = {Yang, Ching-Po and Fu, Chi-Cheng and Sugino, Ken and Liu, Zhiyong and Ren, Qingzhong and Liu, Ling-Yu and Yao, Xiaohao and Lee, Luke P and Lee, Tzumin} } @article {47126, title = {Opposing intrinsic temporal gradients guide neural stem cell production of varied neuronal fates.}, journal = {Science (New York, N.Y.)}, volume = {350}, year = {2015}, month = {2015 Oct 16}, pages = {317-20}, abstract = {

Neural stem cells show age-dependent developmental potentials, as evidenced by their production of distinct neuron types at different developmental times. Drosophila neuroblasts produce long, stereotyped lineages of neurons. We searched for factors that could regulate neural temporal fate by RNA-sequencing lineage-specific neuroblasts at various developmental times. We found that two RNA-binding proteins, IGF-II mRNA-binding protein (Imp) and Syncrip (Syp), display opposing high-to-low and low-to-high temporal gradients with lineage-specific temporal dynamics. Imp and Syp promote early and late fates, respectively, in both a slowly progressing and a rapidly changing lineage. Imp and Syp control neuronal fates in the mushroom body lineages by regulating the temporal transcription factor Chinmo translation. Together, the opposing Imp/Syp gradients encode stem cell age, specifying multiple cell fates within a lineage.

}, issn = {1095-9203}, doi = {10.1126/science.aad1886}, author = {Liu, Zhiyong and Yang, Ching-Po and Sugino, Ken and Fu, Chi-Cheng and Liu, Ling-Yu and Yao, Xiaohao and Lee, Luke P and Lee, Tzumin} }