Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing

Tang, Qin; Iyer, Sowmya; Lobbardi, Riadh; Moore, John C.; Chen, Huidong; Lareau, Caleb A.; Hebert, Christine; Shaw, McKenzie; Neftel, Cyril; Suvà, Mario L.; Ceol, Craig J.; Bernards, André; Aryee, Martin J.; Pinello, Luca; Drummond, Iain A.; Langenau, David M.

doi:10.1084/jem.20170976

Cited by 184 publications

(206 citation statements)

References 52 publications

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“…However, B‐cell transcripts were also found in the lymphoid mpeg1.1 − cell population, suggesting that not all B lymphocytes express mpeg1.1 . To further explore the identity of lymphoid mpeg1.1 + cells, we turned to single‐cell analysis and examined transcript expression among individual hematopoietic cells using our previously reported single‐cell transcriptional profiling of zebrafish WKM . By querying this dataset, we first confirmed the existence of a mpeg1.1 + cluster associated with the B‐cell lineage (Fig.…”

Section: Resultsmentioning

confidence: 87%

“…Whole‐kidney marrows were isolated from three separate adult wild‐type fish (3‐9 mo old) and subjected to inDrop single‐cell RNA sequencing https://molpath.shinyapps.io/zebrafishblood/…”

Section: Methodsmentioning

confidence: 99%

“…Whole-kidney marrows were isolated from three separate adult wildtype fish (3-9 mo old) and subjected to inDrop single-cell RNA sequencing. 30 These data are publicly available at the NCBI GEO database under accession ID GSE100913 and can be accessed directly through the website https://molpath.shinyapps.io/zebrafishblood/…”

Section: Single-cell Transcriptome Analysismentioning

confidence: 99%

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Themacrophage-expressed gene(mpeg)1identifies a subpopulation of B cells in the adult zebrafish

Ferrero

Gomez

lyer

et al. 2020

Journal of Leukocyte Biology

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The mononuclear phagocytic system consists of many cells, in particular macrophages, scattered throughout the body. However, there is increasing evidence for the heterogeneity of tissue‐resident macrophages, leading to a pressing need for new tools to discriminate mononuclear phagocytic system subsets from other hematopoietic lineages. Macrophage‐expressed gene (Mpeg)1.1 is an evolutionary conserved gene encoding perforin‐2, a pore‐forming protein associated with host defense against pathogens. Zebrafish mpeg1.1:GFP and mpeg1.1:mCherry reporters were originally established to specifically label macrophages. Since then more than 100 peer‐reviewed publications have made use of mpeg1.1‐driven transgenics for in vivo studies, providing new insights into key aspects of macrophage ontogeny, activation, and function. Whereas the macrophage‐specific expression pattern of the mpeg1.1 promoter has been firmly established in the zebrafish embryo, it is currently not known whether this specificity is maintained through adulthood. Here we report direct evidence that beside macrophages, a subpopulation of B‐lymphocytes is marked by mpeg1.1 reporters in most adult zebrafish organs. These mpeg1.1+ lymphoid cells endogenously express mpeg1.1 and can be separated from mpeg1.1+ macrophages by virtue of their light‐scatter characteristics using FACS. Remarkably, our analyses also revealed that B‐lymphocytes, rather than mononuclear phagocytes, constitute the main mpeg1.1‐positive population in irf8null myeloid‐defective mutants, which were previously reported to recover tissue‐resident macrophages in adulthood. One notable exception is skin macrophages, whose development and maintenance appear to be independent from irf8, similar to mammals. Collectively, our findings demonstrate that irf8 functions in myelopoiesis are evolutionary conserved and highlight the need for alternative macrophage‐specific markers to study the mononuclear phagocytic system in adult zebrafish.

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Section: Resultsmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Single-cell Transcriptome Analysismentioning

confidence: 99%

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Themacrophage-expressed gene(mpeg)1identifies a subpopulation of B cells in the adult zebrafish

Ferrero

Gomez

lyer

et al. 2020

Journal of Leukocyte Biology

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“…The 50 most significantly differentially expressed genes (Wilcoxon rank-sum test) for the putative T cells include a number of T cell and immune markers (23) ( Figure 3B). We note that we did not observe significant expression of markers associated with other motile non-T immune cells (B cells, macrophages, or neutrophils) (23,24), and we do not find support for NK cells (Materials and Methods, Figure S6).…”

mentioning

confidence: 72%

Heterogeneous T cell motility behaviors emerge from a coupling between speed and turningin vivo

Jerison

Quake

2019

Preprint

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Immune cells carry out dynamic search processes for antigen and pathogens. T cells in vivo migrate primarily via undirected random walks, but it remains unresolved how these random walks generate a characteristic search behavior. Here we use light sheet microscopy to observe the native population of T cells in the larval zebrafish tail and fin fold over long times. We find that cell-to-cell variability is amplified by a correlation between speed and directional persistence, generating a characteristic cell behavioral manifold that is preserved under a perturbation to cell speeds. Our results suggest that speed-persistence coupling may be an intrinsic feature of T cell migration that provides an alternative to Levy flight for accessing a broad range of length scales in vivo.

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“…scRNA-seq successfully distinguished not only the cell types of proximal tubules, loop of Henle, distal tubules, and collecting ducts, but also found that interferon scores based on tubular epithelial cells' scRNA-seq data of lupus nephritis patients correlate with renal clinical scores. Tang et al [75] performed scRNA-seq analysis of zebrafish kidney that was deficient in several genes and investigated the consequence of the gene deficiencies; in addition, they uncovered several novel cell types.…”

Section: Current Studies In the Field Of Kidney Research That Used Scmentioning

confidence: 99%

Understanding the Biology and Pathogenesis of the Kidney by Single-Cell Transcriptomic Analysis

Song

Zhang

et al. 2018

Kidney Dis

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Background: Single-cell RNA-seq (scRNA-seq) has recently emerged as a revolutionary and powerful tool for biomedical research. However, there have been relatively few studies using scRNA-seq in the field of kidney study. Summary: scRNA-seq achieves gene expression profiling at single-cell resolution in contrast with the conventional methods of gene expression profiling, which are based on cell population and give averaged values of gene expression of the cells. Single-cell transcriptomic analysis is crucial because individual cells of the same type are highly heterogeneous in gene expression, which reflects the existence of subpopulations, different cellular states, or molecular dynamics, of the cells, and should be resolved for further insights. In addition, gene expression analysis of tissues or organs that usually comprise multiple cell types or subtypes results in data that are not fully applicable to any given cell type. scRNA-seq is capable of identifying all cell types and subtypes in a tissue, including those that are new or present in small quantity. With these unique capabilities, scRNA-seq has been used to dissect molecular processes in cell differentiation and to trace cell lineages in development. It is also used to analyze the cells in a lesion of disease to identify the cell types and molecular dynamics implicated in the injury. With continuous technical improvement, scRNA-seq has become extremely high throughput and cost effective, making it accessible to all laboratories. In the present review article, we provide an overall review of scRNA-seq concerning its history, improvements, and applications. In addition, we describe the available studies in which scRNA-seq was employed in the field of kidney research. Lastly, we discuss other potential uses of scRNA-seq for kidney research. Key Message: This review article provides general information on scRNA-seq and its various uses. Particularly, we summarize the studies in the field of kidney diseases in which scRNA-seq was used and discuss potential additional uses of scRNA-seq for kidney research.

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Dissecting hematopoietic and renal cell heterogeneity in adult zebrafish at single-cell resolution using RNA sequencing

Cited by 184 publications

References 52 publications

Themacrophage-expressed gene(mpeg)1identifies a subpopulation of B cells in the adult zebrafish

Themacrophage-expressed gene(mpeg)1identifies a subpopulation of B cells in the adult zebrafish

Heterogeneous T cell motility behaviors emerge from a coupling between speed and turningin vivo

Understanding the Biology and Pathogenesis of the Kidney by Single-Cell Transcriptomic Analysis

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