Tristan Qingyun Li

Washington University in St. Louis | WUSTL , Wash U · Department of Neuroscience and Department of Genetics

Microglia and non-parenchymal macrophages in the brain are mononuclear phagocytes that are increasingly recognized to be essential players in the development, homeostasis and diseases of the central nervous system. With the availability of new genetic, molecular and pharmacological tools, considerable advances have been made towards our understandi...

Microglia are increasingly recognized for their major contributions during brain development and neurodegenerative disease. It is currently unknown whether these functions are carried out by subsets of microglia during different stages of development and adulthood or within specific brain regions. Here, we performed deep single-cell RNA sequencing...

Investigating human oligodendrogenesis and the interaction of oligodendrocytes with neurons and astrocytes would accelerate our understanding of the mechanisms underlying white matter disorders. However, this is challenging because of the limited accessibility of functional human brain tissue. Here, we developed a new differentiation method of huma...

Sex is a key modifier of neurological disease outcomes. Microglia are implicated in neurological diseases and modulated by microRNAs, but it is unknown whether microglial microRNAs have sex-specific influences on disease. We show in mice that microglial microRNA expression differs in males and females and that loss of microRNAs leads to sex-specifi...

The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Although an increasing number of interventions show promise for rejuvenation2, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplo...

The hemizygous R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), a microglia-specific gene in the brain, increases risk for late-onset Alzheimer’s disease (AD). Using transcriptomic analysis of single nuclei from brain tissues of patients with AD carrying the R47H mutation or the common variant (CV)–TREM2, we found that R47H...

The hemizygous R47H variant of TREM2, a microglia-specific gene in the brain, increases risk for late-onset Alzheimer's disease (AD). In this study, we identified a subpopulation of microglia with disease-enhancing proinflammatory signatures associated with the R47H mutation in human AD brains and tauopathy mouse brains. Using transcriptomic analys...

Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified—such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function¹—these deleterious processes interact...

Ageing is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death1. Despite rapid advances over recent years, many of the molecular and cellular processes that underlie the progressive loss of healthy physiology are poorly understood2. To gain a better insight into these proc...

Protein aggregation diseases involve intracellular accumulation or extracellular deposition of certain protein species in neuronal or glial cells, leading to neurodegeneration and shortened lifespan. Prime examples include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), which a...

Astrocytes are heterogeneous controlling numerous aspects of brain function. In this issue of Neuron, Huang et al. (2020) uncover a novel role of NFIA, which regulates unique properties of adult hippocampal astrocytes via region-specific DNA binding, thereby modulating the plasticity of local circuits. Astrocytes are heterogeneous controlling numer...

Nervous system function depends on proper myelination for insulation and critical trophic support for axons. Myelination is tightly regulated spatially and temporally, but how it is controlled molecularly remains largely unknown. Here, we identified key molecular mechanisms governing the regional and temporal specificity of CNS myelination. We show...

Here we present a compendium of single-cell transcriptomic data from the model organism Mus musculus that comprises more than 100,000 cells from 20 organs and tissues. These data represent a new resource for cell biology, reveal gene expression in poorly characterized cell populations and enable the direct and controlled comparison of gene expressi...

Microglia are increasingly recognized for their major contributions during brain development and neurodegenerative disease. It is currently unknown if these functions are carried out by subsets of microglia during different stages of development and adulthood or within specific brain regions. Here, we performed deep single-cell RNA sequencing (scRN...

The Tabula Muris Consortium We have created a compendium of single cell transcriptome data from the model organism Mus musculus comprising more than 100,000 cells from 20 organs and tissues. These data represent a new resource for cell biology, revealing gene expression in poorly characterized cell populations and allowing for direct and controlled...

Organisms have evolved strikingly parallel phenotypes in response to similar selection pressures suggesting that there may be shared constraints limiting the possible evolutionary trajectories. For example, the behavioral adaptation of specialist Drosophila species to specific host plants can exhibit parallel changes in their adult olfactory neuroa...

Drosophila uses 50 different olfactory receptor neuron (ORN) classes that are clustered within distinct sensilla subtypes to decipher their chemical environment. Each sensilla subtype houses 1–4 ORN identities that arise through asymmetric divisions of a single sensory organ precursor (SOP). Despite a number of mutational studies investigating the...

Author How do individual neurons know what type of a circuit they must integrate into? To correctly assemble neural circuits during development, the identities of neurons must be coordinated with the identities of the circuits into which they will be integrated. How is this process regulated? We have used the olfactory circuits that regulate sex-s...

Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, the olfactory environment is detected by 50 different olfactory receptor neuron (ORN) classes that are clustered in combinations within distinct sensilla subtypes. Each sensilla subtype houses stereotypically clustered 1-4 ORN identities that a...

Expression of GFP in the mid-pupal antennal lobe driven by Bar or bab1 GAL4. (A) A confocal Z-projection showing neuropil (magenta) and Bar-GAL4 UAS-Syt GFP (green). (B) As in (A) but with bab1-GAL4. Both images were taken from approximately 50 hr APF pupal brains. This data was incorporated into Table 1. (TIF)

Effect of loss of apterous or bar on OR expression. (A) Quantitative RT-PCR analysis for ORs in control (ey-FLP FRT19A/FM6) and bar mutant clones (ey-FLP FRT19A/D(f)1 Bar FRT19A). No significant changes were detected for all ORs tested. (B) Quantitative RT-PCR analysis of w1118 and ap mutants (nap1/apmd544GAL4). The expression of IR31a (ac1), Or85a...

Overexpression of constitutively active EGFR. (A) Quantitative RT-PCR analysis of OR genes in UAS-GFP; rn89GAL4 and UAS-lambda top 4.4/ rn89GAL4 flies. Or67b (ab9), Or13a (ai1), and IR84a (ac4) were downregulated and Or67a (ab10) was upregulated in EGFR overexpressing flies (* p < 0.05, ** p < 0.01). (B) Staining on the control UAS-GFP; rn89GAL4 th...

Expression of PD genes in the antennal disc. (A) ap expression (red) visualized by the enhancer trap line aprK568 remains inside the central fold (compared to Fig 3E and 3F). CF, central fold (dashed line). (B) Confocal images of the third instar larval antennal disc. Bab1 expression is visualized by staining the enhancer trap line bab1A128 with β-...

TF expression in Bar overexpression. (A) and (B) Single slices of 3rd instar larval discs showing the expression patterns of Rn, ap and Dac in control and Bar-overexpressing lines. The central fold is highlighted as a dashed line and is absent in Bar-overexpressing larvae. No change was detected in Rn or ap staining. (C) and (D) Z-stacks of antenna...

Detailed explanation of models presented in Figs 5B, 6A and 7A. This text provides more detailed explanations of how the models in Figs 5B, 6A and 7A were generated. (DOCX)

Expansion of Or47b in Bar overexpression. (A) Quantification of cell counts of Or47b neurons in (B). Flies that overexpress BarH1 with the rn89GAL4 driver show significant reductions in the numbers of Or47b neurons in both females (blue) and males (red). * p < 0.05, ** p < 0.01. (B) Antennal images of Or47b neurons in BarH1 overexpressing flies. Al...

Summary of RNAseq analysis. (A) Venn diagram showing the numbers of genes misregulated in rn mutants in the three early stages T1 (3rd instar larval), T2 (8hr APF), and T3 (40hr APF). APF: after puparium formation. (B) Summary of misregulated genes based on the directions. (TIF)

Heatmap of olfactory receptor expression in the control and rn mutant adult antennae by RNAseq. Normalized expression of all olfactory receptors in the adult stage by DESeq2 is shown. Sequencing results of two biological replicates of paired-end reads per genotype were used as the input. Each transcription variant was treated individually. (TIF)

Expression of Gr5a and Gr43a in rn mutant legs. (Top) The sweet sensing Gr5a neuron (co-expressing Gr61a) is expanded in rn mutants. Control flies have four Gr5a neurons (left, white asterisks) in the 4th and 5th tarsal segments. In rn mutants an ectopic neuron is present (right, red asterisk). (Bottom) The bitter sensing Gr43a neurons are unchange...

Number of Or47b neurons in rn and Bar mutants. Raw data shown in Fig 2A and 2B of the number of Or47b neurons in each antennaa. Single factor ANOVA statistics are displayed at the bottom. (DOCX)

The zinc-finger protein Rotund (Rn) plays a critical role in controlling the development of the fly olfactory system. However, little is known about its molecular function in vivo. Here we added protein tags to the rn locus using CRISPR-Cas9 technology in Drosophila in order to investigate its sub-cellular localization and the genes that it regulat...

With intrinsic acetyltransferase activities, CREB binding protein (CBP)/p300 proteins mediate a variety of physiological events, such as proliferation, differentiation, and apoptosis, by regulating both histones and non-histone proteins. Arabidopsis CBP-type histone acetyltransferase family proteins, HACs, have been found to influence flower by reg...

Epigenetic modifications play a fundamental role in regulating chromatin dynamics and gene expression. The level of histone acetylation is controlled by two functionally antagonistic enzymes, namely histone acetyltransferase (HAT) and histone deacetylase (HDAC). CREB-binding protein (CBP)/p300 proteins, a subfamily of highly conserved HATs, are inv...

Sensory neuron diversity ensures optimal detection of the external world and is a hallmark of sensory systems. An extreme example is the olfactory system, as individual olfactory receptor neurons (ORNs) adopt unique sensory identities by typically expressing a single receptor gene from a large genomic repertoire. In Drosophila, about 50 different O...

During embryonic cell cycles, B-cyclin-CDKs function as the core component of an autonomous oscillator. Current models for the cell-cycle oscillator in nonembryonic cells are slightly more complex, incorporating multiple G1, S phase, and mitotic cyclin-CDK complexes. However, periodic events persist in yeast cells lacking all S phase and mitotic B-...