Macrophage-specific gene functions in Spi1-directed innate immunity

Blood ◽  
2010 ◽  
Vol 116 (3) ◽  
pp. e1-e11 ◽  
Author(s):  
Anna Zakrzewska ◽  
Chao Cui ◽  
Oliver W. Stockhammer ◽  
Erica L. Benard ◽  
Herman P. Spaink ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Target Genes ◽  
Fluorescent Protein ◽  
Myeloid Cells ◽  
Marker Genes ◽  
Specific Gene ◽  
Specific Marker ◽  
Large Set ◽  
Macrophage Migration ◽  
Gene Group

AbstractThe Spi1/Pu.1 transcription factor plays a crucial role in myeloid cell development in vertebrates. Despite extensive studies of Spi1, the controlled gene group remains largely unknown. To identify genes dependent on Spi1, we used a microarray strategy using a knockdown approach in zebrafish embryos combined with fluorescence-activated cell sorting of myeloid cells from transgenic embryos. This approach of using knockdowns with specific green fluorescent protein-marked cell types was highly successful in identifying macrophage-specific genes in Spi1-directed innate immunity. We found a gene group down-regulated on spi1 knockdown, which is also enriched in fluorescence-activated cell-sorted embryonic myeloid cells of a spi1:GFP transgenic line. This gene group, representing putative myeloid-specific Spi1 target genes, contained all 5 previously identified Spi1-dependent zebrafish genes as well as a large set of novel immune-related genes. Colocalization studies with neutrophil and macrophage markers revealed that genes cxcr3.2, mpeg1, ptpn6, and mfap4 were expressed specifically in early embryonic macrophages. In a functional approach, we demonstrated that gene cxcr3.2, coding for chemokine receptor 3.2, is involved in macrophage migration to the site of bacterial infection. Therefore, based on our combined transcriptome analyses, we discovered novel early macrophage-specific marker genes, including a signal transducer pivotal for macrophage migration in the innate immune response.

scholarly journals Discriminative feature of cells characterizes cell populations of interest by a small subset of genes

2021 ◽  
Vol 17 (11) ◽  
pp. e1009579
Author(s):  
Takeru Fujii ◽  
Kazumitsu Maehara ◽  
Masatoshi Fujita ◽  
Yasuyuki Ohkawa
Keyword(s):  
Cell Population ◽  
Single Cells ◽  
Cell Types ◽  
Marker Genes ◽  
Small Subset ◽  
Specific Gene ◽  
Specific Marker ◽  
Cell Characterization ◽  
Discriminative Feature ◽  
Discriminative Approach

Organisms are composed of various cell types with specific states. To obtain a comprehensive understanding of the functions of organs and tissues, cell types have been classified and defined by identifying specific marker genes. Statistical tests are critical for identifying marker genes, which often involve evaluating differences in the mean expression levels of genes. Differentially expressed gene (DEG)-based analysis has been the most frequently used method of this kind. However, in association with increases in sample size such as in single-cell analysis, DEG-based analysis has faced difficulties associated with the inflation of P-values. Here, we propose the concept of discriminative feature of cells (DFC), an alternative to using DEG-based approaches. We implemented DFC using logistic regression with an adaptive LASSO penalty to perform binary classification for discriminating a population of interest and variable selection to obtain a small subset of defining genes. We demonstrated that DFC prioritized gene pairs with non-independent expression using artificial data and that DFC enabled characterization of the muscle satellite/progenitor cell population. The results revealed that DFC well captured cell-type-specific markers, specific gene expression patterns, and subcategories of this cell population. DFC may complement DEG-based methods for interpreting large data sets. DEG-based analysis uses lists of genes with differences in expression between groups, while DFC, which can be termed a discriminative approach, has potential applications in the task of cell characterization. Upon recent advances in the high-throughput analysis of single cells, methods of cell characterization such as scRNA-seq can be effectively subjected to the discriminative methods.

scholarly journals scRNA-sequencing reveals subtype-specific transcriptomic perturbations in DRG neurons of Pirt-EGFPf mice in neuropathic pain condition

2022 ◽  
Author(s):  
Chi Zhang ◽  
Ming-Wen Hu ◽  
Shaoqiu He ◽  
Xuewei Wang ◽  
Xu Cao ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Regeneration ◽  
Target Genes ◽  
Fluorescent Protein ◽  
Pain Treatment ◽  
Maintenance Phase ◽  
Marker Genes ◽  
Drg Neurons ◽  
Soma Size ◽  
Transcriptomic Changes

Functionally distinct subtypes/clusters of dorsal root ganglion (DRG) neurons, which differ in soma size and neurochemical properties, may play different roles in nerve regeneration and pain. However, details about transcriptomic changes in different neuronal subtypes under maladaptive neuropathic pain conditions remain unclear. Chronic constriction injury (CCI) of the sciatic nerve represents a well-established model of neuropathic pain that mimics the etiology of clinical conditions. Therefore, we conducted single-cell RNA-sequencing (scRNA-seq) to characterize subtype-specific perturbations of transcriptomes in lumbar DRG neurons 7 days after sciatic CCI. By using Pirt-EGFPf mice that selectively express enhanced green fluorescent protein in DRG neurons, we established a highly efficient purification process to enrich neurons for scRNA-seq. We observed a loss of marker genes in injured neurons of 12 standard neuronal clusters, and the emergence of four prominent CCI-induced clusters at this peak-maintenance phase of neuropathic pain. Importantly, a portion of injured neurons from a subset of the 12 standard clusters (NP1, PEP5, NF1, and NF2) were spared from injury-induced identity loss, suggesting subtype-specific transcriptomic changes in injured neurons. Moreover, uninjured neurons, which are necessary for mediating the evoked pain, also demonstrated subtype-specific transcriptomic perturbations in these clusters, but not others. Notably, male and female mice showed differential transcriptomic changes in multiple neuronal clusters after CCI, suggesting transcriptomic sexual dimorphism in primary sensory neurons after nerve injury. Collectively, these findings may contribute to the identification of new target genes and development of DRG neuron subtype-specific therapies for optimizing neuropathic pain treatment and nerve regeneration.

scholarly journals Cross-laboratory analysis of brain cell type transcriptomes with applications to interpretation of bulk tissue data

2016 ◽  
Author(s):  
B. Ogan Mancarci ◽  
Lilah Toker ◽  
Shreejoy J Tripathy ◽  
Brenna Li ◽  
Brad Rocco ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Types ◽  
Brain Cell ◽  
Marker Genes ◽  
Specific Gene ◽  
Published Data ◽  
Specific Marker ◽  
Cell Type ◽  
Cell Type Specific ◽  
Bulk Tissue

AbstractEstablishing the molecular diversity of cell types is crucial for the study of the nervous system. We compiled a cross-laboratory database of mouse brain cell type-specific transcriptomes from 36 major cell types from across the mammalian brain using rigorously curated published data from pooled cell type microarray and single cell RNA-sequencing studies. We used these data to identify cell type-specific marker genes, discovering a substantial number of novel markers, many of which we validated using computational and experimental approaches. We further demonstrate that summarized expression of marker gene sets in bulk tissue data can be used to estimate the relative cell type abundance across samples. To facilitate use of this expanding resource, we provide a user-friendly web interface at Neuroexpresso.org.Significance StatementCell type markers are powerful tools in the study of the nervous system that help reveal properties of cell types and acquire additional information from large scale expression experiments. Despite their usefulness in the field, known marker genes for brain cell types are few in number. We present NeuroExpresso, a database of brain cell type specific gene expression profiles, and demonstrate the use of marker genes for acquiring cell type specific information from whole tissue expression. The database will prove itself as a useful resource for researchers aiming to reveal novel properties of the cell types and aid both laboratory and computational scientists to unravel the cell type specific components of brain disorders.

scholarly journals ZNF536, a Novel Zinc Finger Protein Specifically Expressed in the Brain, Negatively Regulates Neuron Differentiation by Repressing Retinoic Acid-Induced Gene Transcription

2009 ◽  
Vol 29 (13) ◽  
pp. 3633-3643 ◽  
Author(s):  
Zhen Qin ◽  
Fangli Ren ◽  
Xialian Xu ◽  
Yongming Ren ◽  
Hongge Li ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Neuronal Differentiation ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Marker Genes ◽  
Specific Gene ◽  
Specific Marker ◽  
Neuron Differentiation ◽  
Finger Protein ◽  
The Brain

ABSTRACT Neuronal differentiation is tightly regulated by a variety of factors. In a search for neuron-specific genes, we identified a highly conserved novel zinc finger protein, ZNF536. We observed that ZNF536 is most abundant in the brain and, in particular, is expressed in the developing central nervous system and dorsal root ganglia and localized in the cerebral cortex, hippocampus, and hypothalamic area. During neuronal differentiation of P19 cells induced by retinoic acid (RA), ZNF536 expression is increased at an early stage, and it is maintained at a constant level in later stages. Overexpression of ZNF536 results in an inhibition of RA-induced neuronal differentiation, while depletion or mutation of the ZNF536 gene results in an enhancement of differentiation. We further demonstrated that ZNF536 inhibits expression of neuron-specific marker genes, possibly through the inhibition of RA response element-mediated transcriptional activity, as overexpression of RA receptor α can rescue the inhibitory role of ZNF536 in neuronal differentiation and neuron-specific gene expression. Our studies have identified a novel zinc finger protein that negatively regulates neuron differentiation.

scholarly journals Identification of Biomarkers Controlling Cell Fate In Blood Cell Development

2021 ◽  
Vol 1 ◽  
Author(s):  
Maryam Nazarieh ◽  
Marc Hoeppner ◽  
Volkhard Helms
Keyword(s):  
Blood Cell ◽  
Cell Fate ◽  
Gene Networks ◽  
Target Genes ◽  
Developmental Stages ◽  
Cell Formation ◽  
Cell Lineage ◽  
Marker Genes ◽  
Specific Marker ◽  
Regulatory Pathways

A blood cell lineage consists of several consecutive developmental stages starting from the pluri- or multipotent stem cell to a state of terminal differentiation. Despite their importance for human biology, the regulatory pathways and gene networks that govern these differentiation processes are not yet fully understood. This is in part due to challenges associated with delineating the interactions between transcription factors (TFs) and their corresponding target genes. A possible step forward in this case is provided by the increasing amount of expression data, as a basis for linking differentiation stages and gene activities. Here, we present a novel hierarchical approach to identify characteristic expression peak patterns that global regulators excert along the differentiation path of cell lineages. Based on such simple patterns, we identified cell state-specific marker genes and extracted TFs that likely drive their differentiation. Integration of the mean expression values of stage-specific “key player” genes yielded a distinct peaking pattern for each lineage that was used to identify further genes in the dataset which behave similarly. Incorporating the set of TFs that regulate these genes led to a set of stage-specific regulators that control the biological process of cell fate. As proof of concept, we considered two expression datasets covering key differentiation events in blood cell formation of mice.

scholarly journals The mutL Gene as a Genome-Wide Taxonomic Marker for High Resolution Discrimination of Lactiplantibacillus plantarum and Its Closely Related Taxa

2021 ◽  
Vol 9 (8) ◽  
pp. 1570
Author(s):  
Chien-Hsun Huang ◽  
Chih-Chieh Chen ◽  
Yu-Chun Lin ◽  
Chia-Hsuan Chen ◽  
Ai-Yun Lee ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Target Genes ◽  
Marker Genes ◽  
Rrna Gene ◽  
Accurate Identification ◽  
Discrimination Power ◽  
Sequence Identity ◽  
Genome Wide ◽  
A Genome

The current taxonomy of the Lactiplantibacillus plantarum group comprises of 17 closely related species that are indistinguishable from each other by using commonly used 16S rRNA gene sequencing. In this study, a whole-genome-based analysis was carried out for exploring the highly distinguished target genes whose interspecific sequence identity is significantly less than those of 16S rRNA or conventional housekeeping genes. In silico analyses of 774 core genes by the cano-wgMLST_BacCompare analytics platform indicated that csbB, morA, murI, mutL, ntpJ, rutB, trmK, ydaF, and yhhX genes were the most promising candidates. Subsequently, the mutL gene was selected, and the discrimination power was further evaluated using Sanger sequencing. Among the type strains, mutL exhibited a clearly superior sequence identity (61.6–85.6%; average: 66.6%) to the 16S rRNA gene (96.7–100%; average: 98.4%) and the conventional phylogenetic marker genes (e.g., dnaJ, dnaK, pheS, recA, and rpoA), respectively, which could be used to separat tested strains into various species clusters. Consequently, species-specific primers were developed for fast and accurate identification of L. pentosus, L. argentoratensis, L. plantarum, and L. paraplantarum. During this study, one strain (BCRC 06B0048, L. pentosus) exhibited not only relatively low mutL sequence identities (97.0%) but also a low digital DNA–DNA hybridization value (78.1%) with the type strain DSM 20314T, signifying that it exhibits potential for reclassification as a novel subspecies. Our data demonstrate that mutL can be a genome-wide target for identifying and classifying the L. plantarum group species and for differentiating novel taxa from known species.

scholarly journals scSorter: assigning cells to known cell types according to marker genes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hongyu Guo ◽  
Jun Li
Keyword(s):  
Real Data ◽  
Cell Types ◽  
Exact Expression ◽  
Marker Genes ◽  
Specific Marker ◽  
Sequencing Data ◽  
Reference Dataset ◽  
Over Expression ◽  
Higher Power ◽  
Cell Type Specific

AbstractOn single-cell RNA-sequencing data, we consider the problem of assigning cells to known cell types, assuming that the identities of cell-type-specific marker genes are given but their exact expression levels are unavailable, that is, without using a reference dataset. Based on an observation that the expected over-expression of marker genes is often absent in a nonnegligible proportion of cells, we develop a method called scSorter. scSorter allows marker genes to express at a low level and borrows information from the expression of non-marker genes. On both simulated and real data, scSorter shows much higher power compared to existing methods.

scholarly journals Emerin Represses STAT3 Signaling through Nuclear Membrane-Based Spatial Control

2021 ◽  
Vol 22 (13) ◽  
pp. 6669
Author(s):  
Byongsun Lee ◽  
Seungjae Lee ◽  
Younggwang Lee ◽  
Yongjin Park ◽  
Jaekyung Shim
Keyword(s):  
Muscular Dystrophy ◽  
Nuclear Membrane ◽  
Target Genes ◽  
Janus Kinase ◽  
C2c12 Cells ◽  
Specific Gene ◽  
Lamin A ◽  
Stat3 Signaling ◽  
Exact Function ◽  
Muscle Homeostasis

Emerin is the inner nuclear membrane protein involved in maintaining the mechanical integrity of the nuclear membrane. Mutations in EMD encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD). There has been accumulating evidence that emerin regulation of specific gene expression is associated with this disease, but the exact function of emerin has still less revealing. Here, we have shown that emerin downregulates signal transducers and activators of transcription 3 (STAT3) signaling, activated exclusively by Janus-kinase (JAK). Deletion mutation experiments showed that the lamin-binding domain of emerin is essential for the inhibition of STAT3 signaling. Emerin interacted directly and co-localized with STAT3 in the nuclear membrane. Emerin knockdown induced STAT3 target genes Bcl2 and Survivin to increase cell survival signals and suppress hydrogen peroxide-induced cell death in HeLa cells. Specifically, downregulation of BAF or lamin A/C increases STAT3 signaling, suggesting that correct-localized emerin by assembling with BAF and lamin A/C acts as an intrinsic inhibitor against STAT3 signaling. In C2C12 cells, emerin knockdown induced STAT3 target gene, Pax7, and activated abnormal myoblast proliferation associated with muscle wasting in skeletal muscle homeostasis. Our results indicate that emerin downregulates STAT3 signaling by inducing retention of STAT3 and delaying STAT3 signaling in the nuclear membrane. This mechanism provides clues to the etiology of emerin-related muscular dystrophy and could be a new therapeutic target for treatment.

ATAK™ receptors, harnessing innate immunity to program myeloid cells to kill cancer

Cytotherapy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. S96
Author(s):  
Y. Wang ◽  
N. Diwanji ◽  
T. Nicholson ◽  
S. Mukherjee ◽  
D. Getts
Keyword(s):  
Innate Immunity ◽  
Myeloid Cells
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