Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immune cell types

ABSTRACTStopping COVID-19 is a priority worldwide. Understanding which cell types are targeted by SARS-CoV-2 virus, whether interspecies differences exist, and how variations in cell state influence viral entry is fundamental for accelerating therapeutic and preventative approaches. In this endeavor, we profiled the transcriptome of nine tissues from a Macaca fascicularis monkey at single-cell resolution. The distribution of SARS-CoV-2 facilitators, ACE2 and TMRPSS2, in different cell subtypes showed substantial heterogeneity across lung, kidney, and liver. Through co-expression analysis, we identified immunomodulatory proteins such as IDO2 and ANPEP as potential SARS-CoV-2 targets responsible for immune cell exhaustion. Furthermore, single-cell chromatin accessibility analysis of the kidney unveiled a plausible link between IL6-mediated innate immune responses aiming to protect tissue and enhanced ACE2 expression that could promote viral entry. Our work constitutes a unique resource for understanding the physiology and pathophysiology of two phylogenetically close species, which might guide in the development of therapeutic approaches in humans.Bullet pointsWe generated a single-cell transcriptome atlas of 9 monkey tissues to study COVID-19.ACE2+TMPRSS2+ epithelial cells of lung, kidney and liver are targets for SARS-CoV-2.ACE2 correlation analysis shows IDO2 and ANPEP as potential therapeutic opportunities.We unveil a link between IL6, STAT transcription factors and boosted SARS-CoV-2 entry.

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Single-cell transcriptome analysis identifies distinct cell types and niche signaling in a primary gastric organoid model

Scientific Reports ◽

10.1038/s41598-019-40809-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Jiamin Chen ◽

Billy T. Lau ◽

Noemi Andor ◽

Susan M. Grimes ◽

Christine Handy ◽

...

Keyword(s):

Single Cell ◽

Transcriptome Analysis ◽

Cell Types ◽

Distinct Cell ◽

Cell Transcriptome ◽

Single Cell Transcriptome

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High-throughput single-cell transcriptome analysis of immune cells from HIV-1 infected individuals before and after therapy

Journal of Virus Eradication ◽

10.1016/s2055-6640(20)30548-3 ◽

2017 ◽

Vol 3 ◽

pp. 31

Author(s):

T. Bradley ◽

C. Hart ◽

B. Hora ◽

J. Pollara ◽

E.P. Browne ◽

...

Keyword(s):

Single Cell ◽

High Throughput ◽

Immune Cells ◽

Transcriptome Analysis ◽

Before And After ◽

Cell Transcriptome ◽

Single Cell Transcriptome ◽

Hiv 1

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A Single-Cell Transcriptome Profiling of Anterior Kidney Leukocytes From Nile Tilapia (Oreochromis niloticus)

Frontiers in Immunology ◽

10.3389/fimmu.2021.783196 ◽

2021 ◽

Vol 12 ◽

Author(s):

Liting Wu ◽

Along Gao ◽

Lan Li ◽

Jianlin Chen ◽

Jun Li ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

B Cell ◽

Single Cell ◽

Nile Tilapia ◽

Immune Cell ◽

Cell Types ◽

Cell Transcriptome ◽

B Cell Subsets ◽

Single Cell Transcriptome

Teleost fish anterior kidney (AK) is an important hematopoietic organ with multifarious immune cells, which have immune functions comparable to mammalian bone marrow. Myeloid and lymphoid cells locate in the AK, but the lack of useful specific gene markers and antibody-based reagents for the cell subsets makes the identification of the different cell types difficult. Single-cell transcriptome sequencing enables single-cell capture and individual library construction, making the study on the immune cell heterogeneity of teleost fish AK possible. In this study, we examined the transcriptional patterns of 11,388 AK leukocytes using 10× Genomics single-cell RNA sequencing (scRNA-seq). A total of 22 clusters corresponding to five distinct immune cell subsets were identified, which included B cells, T cells, granulocytes, macrophages, and dendritic cells (DCs). However, the subsets of myeloid cells (granulocytes, macrophages, and DCs) were not identified in more detail according to the known specific markers, even though significant differences existed among the clusters. Thereafter, we highlighted the B-cell subsets and identified them as pro/pre B cells, immature/mature B cells, activated B/plasmablasts, or plasma cells based on the different expressions of the transcription factors (TFs) and cytokines. Clustering of the differentially modulated genes by pseudo-temporal trajectory analysis of the B-cell subsets showed the distinct kinetics of the responses of TFs to cell conversion. Moreover, we classified the T cells and discovered that CD3+CD4−CD8−, CD3+CD4+CD8+, CD4+CD8−, and CD4−CD8+ T cells existed in AK, but neither CD4+CD8− nor CD4−CD8+ T cells can be further classified into subsets based on the known TFs and cytokines. Pseudotemporal analysis demonstrated that CD4+CD8− and CD4−CD8+ T cells belonged to different states with various TFs that might control their differentiation. The data obtained above provide a valuable and detailed resource for uncovering the leukocyte subsets in Nile tilapia AK, as well as more potential markers for identifying the myeloid and lymphoid cell types.

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Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans

10.1101/638254 ◽

2019 ◽

Author(s):

Ying Hu ◽

Mohini Ranganathan ◽

Chang Shu ◽

Xiaoyu Liang ◽

Suhas Ganesh ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Single Cell ◽

Immune Cells ◽

Cell Types ◽

Gene Set Enrichment Analysis ◽

Cell Type ◽

Cell Type Specific ◽

Cell Transcriptome ◽

Single Cell Transcriptome

AbstractDelta 9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, is also known to modulate immune response in peripheral cells. The mechanisms of THC’s effects on gene expression in human immune cells remains poorly understood. Combining a within-subject design with single cell transcriptome mapping, we report that administration of THC acutely alters gene expression in 15,973 human blood immune cells. Controlled for high inter-individual transcriptomic variability, we identified 294 transcriptome-wide significant genes among eight cell types including 69 common genes and 225 cell-type specific genes affected by acute THC administration, including those genes involving not only in immune response, cytokine production, but signal transduction, and cell proliferation and apoptosis. We revealed distinct transcriptomic sub-clusters affected by THC in major immune cell types where THC perturbed cell type-specific intracellular gene expression correlations. Gene set enrichment analysis further supports the findings of THC’s common and cell-type specific effects on immune response and cell toxicity. We found that THC alters the correlation of cannabinoid receptor gene, CNR2, with other genes in B cells, in which CNR2 showed the highest level of expression. This comprehensive cell-specific transcriptomic profiling identified novel genes regulated by THC and provides important insights into THC’s acute effects on immune function that may have important medical implications.

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