Dynamics of gene expression in single root cells ofA. thaliana

ABSTRACTSingle-cell RNA-seq can yield high-resolution cell-type-specific expression signatures that reveal new cell types and the developmental trajectories of cell lineages. Here, we apply this approach toA. thalianaroot cells to capture gene expression in 3,121 root cells. We analyze these data with Monocle 3, which orders single cell transcriptomes in an unsupervised manner and uses machine learning to reconstruct single-cell developmental trajectories along pseudotime. We identify hundreds of genes with cell-type-specific expression, with pseudotime analysis of several cell lineages revealing both known and novel genes that are expressed along a developmental trajectory. We identify transcription factor motifs that are enriched in early and late cells, together with the corresponding candidate transcription factors that likely drive the observed expression patterns. We assess and interpret changes in total RNA expression along developmental trajectories and show that trajectory branch points mark developmental decisions. Finally, by applying heat stress to whole seedlings, we address the longstanding question of possible heterogeneity among cell types in the response to an abiotic stress. Although the response of canonical heat shock genes dominates expression across cell types, subtle but significant differences in other genes can be detected among cell types. Taken together, our results demonstrate that single-cell transcriptomics holds promise for studying plant development and plant physiology with unprecedented resolution.

Download Full-text

Cell-type Specific Expression Quantitative Trait Loci Associated with Alzheimer Disease in Blood and Brain Tissue

10.1101/2020.11.23.20237008 ◽

2020 ◽

Author(s):

Devanshi Patel ◽

Xiaoling Zhang ◽

John J. Farrell ◽

Jaeyoon Chung ◽

Thor D. Stein ◽

...

Keyword(s):

Gene Expression ◽

Quantitative Trait ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Cell Types ◽

Eqtl Analysis ◽

Cell Type ◽

Specific Expression ◽

Cell Type Specific Expression ◽

Cell Type Specific

ABSTRACTBecause regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell-types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5,257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1Mb of genes was evaluated using linear regression models for unrelated subjects and linear mixed models for related subjects. Cell type-specific eQTL (ct-eQTL) models included an interaction term for expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2,533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell-types is supported by the observation that a large portion of GWS ct-eQTLs map within 1Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type specific analysis.

Download Full-text

Single-cell RNA-sequencing reveals thoracolumbar vertebra heterogeneity and rib-genesis in pigs

10.1101/2021.05.25.445704 ◽

2021 ◽

Author(s):

Jianbo Li ◽

Ligang Wang ◽

Dawei Yu ◽

Junfeng Hao ◽

Longchao Zhang ◽

...

Keyword(s):

Gene Expression ◽

Single Cell ◽

Lumbar Vertebra ◽

Cell Types ◽

Cell Type ◽

Specific Expression ◽

Coupled Process ◽

Gene Expression Dynamics ◽

Cell Type Specific ◽

Thoracolumbar Vertebra

Thoracolumbar vertebra (TLV) and rib primordium (RP) development is a common evolutionary feature across vertebrates although whole-organism analysis of TLV and RP gene expression dynamics has been lacking. Here we investigated the single-cell transcriptomic landscape of thoracic vertebra (TV), lumbar vertebra (LV), and RP cells from a pig embryo at 27 days post-fertilization (dpf) and identified six cell types with distinct gene-expression signatures. In-depth dissection of the gene-expression dynamics and RNA velocity revealed a coupled process of osteogenesis and angiogenesis during TLV and rib development. Further analysis of cell-type-specific and strand-specific expression uncovered the extremely high levels of HOXA10 3'-UTR sequence specific to osteoblast of LV cells, which may function as anti-HOXA10-antisense by counteracting the HOXA10-antisense effect to determine TLV transition. Thus, this work provides a valuable resource for understanding embryonic osteogenesis and angiogenesis underlying vertebrate TLV and RP development at the cell-type-specific resolution, which serves as a comprehensive view on the transcriptional profile of animal embryo development.

Download Full-text

Single-Cell Regulatory Network Inference and Clustering Identifies Cell-Type Specific Expression Pattern of Transcription Factors in Mouse Sciatic Nerve

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.676515 ◽

2021 ◽

Vol 15 ◽

Author(s):

Mingchao Li ◽

Qing Min ◽

Matthew C. Banton ◽

Xinpeng Dun

Keyword(s):

Transcription Factors ◽

Sciatic Nerve ◽

Single Cell ◽

Cell Types ◽

Cell Type ◽

Specific Expression ◽

Single Cell Rna Sequencing ◽

Cell Type Specific Expression ◽

Cell Type Specific ◽

Different Cell Types

Advances in single-cell RNA sequencing technologies and bioinformatics methods allow for both the identification of cell types in a complex tissue and the large-scale gene expression profiling of various cell types in a mixture. In this report, we analyzed a single-cell RNA sequencing (scRNA-seq) dataset for the intact adult mouse sciatic nerve and examined cell-type specific transcription factor expression and activity during peripheral nerve homeostasis. In total, we identified 238 transcription factors expressed in nine different cell types of intact mouse sciatic nerve. Vascular smooth muscle cells have the lowest number of transcription factors expressed with 17 transcription factors identified. Myelinating Schwann cells (mSCs) have the highest number of transcription factors expressed, with 61 transcription factors identified. We created a cell-type specific expression map for the identified 238 transcription factors. Our results not only provide valuable information about the expression pattern of transcription factors in different cell types of adult peripheral nerves but also facilitate future studies to understand the function of key transcription factors in the peripheral nerve homeostasis and disease.

Download Full-text

Changing Patterns of Gene Expression in Dictyostelium Prestalk Cell Subtypes Recognized by In Situ Hybridization with Genes from Microarray Analyses

Eukaryotic Cell ◽

10.1128/ec.2.3.627-637.2003 ◽

2003 ◽

Vol 2 (3) ◽

pp. 627-637 ◽

Cited By ~ 57

Author(s):

Mineko Maeda ◽

Haruyo Sakamoto ◽

Negin Iranfar ◽

Danny Fuller ◽

Toshinari Maruo ◽

...

Keyword(s):

Gene Expression ◽

In Situ Hybridization ◽

Cell Types ◽

Cell Type ◽

Developmentally Regulated ◽

Specific Expression ◽

Cell Type Specific Expression ◽

Changing Patterns ◽

Cell Type Specific

ABSTRACT We used microarrays carrying most of the genes that are developmentally regulated in Dictyostelium to discover those that are preferentially expressed in prestalk cells. Prestalk cells are localized at the front of slugs and play crucial roles in morphogenesis and slug migration. Using whole-mount in situ hybridization, we were able to verify 104 prestalk genes. Three of these were found to be expressed only in cells at the very front of slugs, the PstA cell type. Another 10 genes were found to be expressed in the small number of cells that form a central core at the anterior, the PstAB cell type. The rest of the prestalk-specific genes are expressed in PstO cells, which are found immediately posterior to PstA cells but anterior to 80% of the slug that consists of prespore cells. Half of these are also expressed in PstA cells. At later stages of development, the patterns of expression of a considerable number of these prestalk genes changes significantly, allowing us to further subdivide them. Some are expressed at much higher levels during culmination, while others are repressed. These results demonstrate the extremely dynamic nature of cell-type-specific expression in Dictyostelium and further define the changing physiology of the cell types. One of the signals that affect gene expression in PstO cells is the hexaphenone DIF-1. We found that expression of about half of the PstO-specific genes were affected in a mutant that is unable to synthesize DIF-1, while the rest appeared to be DIF independent. These results indicate that differentiation of some aspects of PstO cells can occur in the absence of DIF-1.

Download Full-text

Cnidarian cell type diversity revealed by whole-organism single-cell RNA-seq analysis

10.1101/201103 ◽

2017 ◽

Author(s):

Arnau Sebé-Pedrós ◽

Elad Chomsky ◽

Baptiste Saudememont ◽

Marie-Pierre Mailhe ◽

Flora Pleisser ◽

...

Keyword(s):

Single Cell ◽

Cell Types ◽

Tissue Level ◽

Rna Seq ◽

Cell Type ◽

Specific Expression ◽

Animal Evolution ◽

Neuronal Markers ◽

Cell Type Specific Expression ◽

Cell Type Specific

A hallmark of animal evolution is the emergence and diversification of cell type-specific transcriptional states. But systematic and unbiased characterization of differentiated gene regulatory programs was so far limited to specific tissues in a few model species. Here, we perform whole-organism single cell transcriptomics to map cell types in the cnidarian Nematostella vectensis, a non-bilaterian animal that display complex tissue-level bodyplan organization. We uncover high diversity of transcriptional states in Nematostella, demonstrating cell type-specific expression for 35% of the genes and 51% of the transcription factors (TFs) detected. We identify eight broad cell clusters corresponding to cell classes such as neurons, muscles, cnidocytes, or digestive cells. These clusters comprise multiple cell modules expressing diverse and specific markers, uncovering in particular a rich repertoire of cells associated with neuronal markers. TF expression and sequence analysis defines the combinatorial code that underlies this cell-specific expression. It also reveals the existence of a complex regulatory lexicon of TF binding motifs encoded at both enhancer and promoters of Nematostella tissue-specific genes. Whole organism single cell RNA-seq is thereby established as a tool for comprehensive study of genome regulation and cell type evolution.

Download Full-text

Cell-type-specific expression quantitative trait loci associated with Alzheimer disease in blood and brain tissue

Translational Psychiatry ◽

10.1038/s41398-021-01373-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Devanshi Patel ◽

Xiaoling Zhang ◽

John J. Farrell ◽

Jaeyoon Chung ◽

Thor D. Stein ◽

...

Keyword(s):

Gene Expression ◽

Quantitative Trait ◽

Expression Patterns ◽

Regulation Of Gene Expression ◽

Cell Types ◽

Eqtl Analysis ◽

Cell Type ◽

Specific Expression ◽

Cell Type Specific Expression ◽

Cell Type Specific

AbstractBecause regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1 Mb of genes was evaluated using linear regression models for unrelated subjects and linear-mixed models for related subjects. Cell-type-specific eQTL (ct-eQTL) models included an interaction term for the expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell types is supported by the observation that a large portion of GWS ct-eQTLs map within 1 Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type-specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type-specific analysis.

Download Full-text