Mapping the Mouse Cell Atlas by Microwell-Seq

Han, Xiaoping; Wang, Renying; Zhou, Yincong; Fei, Lijiang; Sun, Huiyu; Lai, Shih‐Wei; Saadatpour, Assieh; Zhou, Ziyu; Chen, Haide; Ye, Fang; Huang, Daosheng; Xu, Yang; Huang, Wentao; Jiang, Mengmeng; Jiang, Xinyi; Mao, Jie; Chen, Yao; Lu, Chenyu; Xie, Jin; Fang, Qun; Wang, Yibin; Yue, Rui; Li, Tiefeng; Huang, He; Orkin, Stuart H.; Yuan, Guo‐Cheng; Chen, Ming; Guo, Guoji

doi:10.1016/j.cell.2018.02.001

Cited by 1,209 publications

(1,013 citation statements)

References 62 publications

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“…LincRNA-Cox2 is highly expressed in the lung in a very cell type-specific manner (Figures S1B and S1C). Using the Mouse Cell Atlas generated by Han et al, 2018, we can show the differences in cell type expression between Ptgs2 and lincRNA-Cox2 (Figure S1B). Overall, lincRNA-Cox2 has a higher expression in specific immune- related cells in the lung, whereas Ptgs2 has higher expression in epithelial and endothelial cells, providing additional evidence that lincRNA-Cox2 has distinct roles in trans independent of its regulation of Ptgs2.…”

Section: Resultsmentioning

confidence: 99%

Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2

et al. 2018

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SUMMARY An inducible gene expression program is a hallmark of the host inflammatory response. Recently, long intergenic non-coding RNAs (lincRNAs) have been shown to regulate the magnitude, duration, and resolution of these responses. Among these is lincRNA- Cox2, a dynamically regulated gene that broadly controls immune gene expression. To evaluate the in vivo functions of this lincRNA, we characterized multiple models of lincRNA-Cox2-deficient mice. LincRNA- Cox2-deficient macrophages and murine tissues had altered expression of inflammatory genes. Tran- scriptomic studies from various tissues revealed that deletion of the lincRNA-Cox2 locus also strongly impaired the basal and inducible expression of the neighboring gene prostaglandin-endoperoxide synthase (Ptgs2), encoding cyclooxygenase-2, a key enzyme in the prostaglandin biosynthesis pathway. By utilizing different genetic manipulations in vitro and in vivo, we found that lincRNA-Cox2 functions through an enhancer RNA mechanism to regulate Ptgs2. More importantly, lincRNA-Cox2 also functions in trans, independently of Ptgs2, to regulate critical innate immune genes in vivo.

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Section: Resultsmentioning

confidence: 99%

Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2

et al. 2018

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“…High-throughput single-cell RNA-seq (scRNA-seq) now enables RNA profiling in thousands of individual cells in complex tissue (Han et al, 2018; Klein et al, 2015; Macosko et al, 2015; Rosenberg et al, 2018; Zheng et al, 2017). To date, single-cell gene expression studies have yielded cell-type classifications in the mouse cerebral cortex (Tasic et al, 2016; Zeisel et al, 2015), retina (Shekhar et al, 2016), hypothalamic arcuate nucleus (Campbell et al, 2017), entopeduncular nucleus (Wallace et al, 2017) and amygdala (Wu et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain

Saunders

Macosko

Wysoker

et al. 2018

Cell

1,440

118

1,757

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The mammalian brain is composed of diverse, specialized cell populations. To systematically ascertain and learn from these cellular specializations, we used Drop-seq to profile RNA expression in 690,000 individual cells sampled from 9 regions of the adult mouse brain. We identified 565 transcriptionally distinct groups of cells using computational approaches developed to distinguish biological from technical signals. Cross-region analysis of these 565 cell populations revealed features of brain organization, including a gene-expression module for synthesizing axonal and presynaptic components, patterns in the co-deployment of voltage-gated ion channels, functional distinctions among the cells of the vasculature and specialization of glutamatergic neurons across cortical regions. Systematic neuronal classifications for two complex basal ganglia nuclei and the striatum revealed a rare population of spiny projection neurons. This adult mouse brain cell atlas, accessible through interactive online software (DropViz), serves as a reference for development, disease, and evolution.

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“…The relative scales and sources of variability are very important to understand in the modern world of single‐cell highly multiplexed measurements. These new technologies are revealing the complex structure of “cell space” with cells occupying a large array of types (Han et al , ; Rosenberg et al , ; Tabula Muris Consortium et al , ), states (Trapnell, ; Cheng et al , ), and fronts (Shoval et al , ) that reflect functional stratification. Despite our knowledge that cell types and states manifest as gene expression heterogeneity, sometimes total gene expression variability is interpreted as arising from two‐state transcriptional bursting alone (Larsson et al , ).…”

Section: Introductionmentioning

confidence: 99%

Mammalian gene expression variability is explained by underlying cell state

Foreman

Wollman

2020

Molecular Systems Biology

120

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Gene expression variability in mammalian systems plays an important role in physiological and pathophysiological conditions. This variability can come from differential regulation related to cell state (extrinsic) and allele‐specific transcriptional bursting (intrinsic). Yet, the relative contribution of these two distinct sources is unknown. Here, we exploit the qualitative difference in the patterns of covariance between these two sources to quantify their relative contributions to expression variance in mammalian cells. Using multiplexed error robust RNA fluorescent in situ hybridization (MERFISH), we measured the multivariate gene expression distribution of 150 genes related to Ca2+ signaling coupled with the dynamic Ca2+ response of live cells to ATP. We show that after controlling for cellular phenotypic states such as size, cell cycle stage, and Ca2+ response to ATP, the remaining variability is effectively at the Poisson limit for most genes. These findings demonstrate that the majority of expression variability results from cell state differences and that the contribution of transcriptional bursting is relatively minimal.

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Mapping the Mouse Cell Atlas by Microwell-Seq

Cited by 1,209 publications

References 62 publications

Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2

Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2

Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain

Mammalian gene expression variability is explained by underlying cell state

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