scholarly journals Astrocyte-like glia-specific gene deathstar is crucial for normal development, adult locomotion and lifespan of male Drosophila

2020 ◽  
Author(s):  
Hadi Najafi ◽  
Kyle Wong ◽  
Woo Jae Kim

Abstract Background Drosophila melanogaster is a proper model organism for studying the development and function of the nervous system. The Drosophila nervous system consists of distinct cell types with significant homologies to various cell types of more advanced organisms, including human. Among all cell types of the nervous system, astrocyte-like glia (ALG) have conserved functions to mammals and are essential for normal physiology and behaviours of the fly. Results In this study, we exploited the gene expression profile of single cells in Drosophila optic lobe to identify the genes with specific expression pattern in each cell type. Through a bioinformatical analysis of the data, a novel ALG-specific gene (here assigned as deathstar ) was identified. Immunostaining of deathstar in the central nervous system (CNS) showed its presence in specific regions of Drosophila ventral nerve cord, which previously has been characterized as ALG cells. Consistent with the bioinformatical analysis, deathstar -related signals were overlapped with the signals of the previously-reported ALG marker, Eaat1 , supporting its specific expression in ALG cells. At the physiological level, RNAi-mediated suppression of deathstar gene impeded the normal development of male flies without any effects on females. Cell type-specific expression of deathstar RNAi showed that deathstar gene affects locomotion behaviour and lifespan of D. melanogaster , in an ALG-specific manner. Conclusions Taken together, we showed that bioinformatical analysis of a previously reported expression data of Drosophila optic lobe successfully predicted the ALG-specific expression pattern of deathstar gene. Moreover, it was consistent with the ALG-specific effects of this gene on locomotion and lifespan of D. melanogaster, in vivo .

2019 ◽  
Author(s):  
Hadi Najafi ◽  
Kyle Wong ◽  
Woo Jae Kim

ABSTRACTDrosophila melanogaster is a proper model organism for studying the development and function of the nervous system. The Drosophila nervous system consists of distinct cell types with significant homologies to various cell types of more advanced organisms, including human. Among all cell types of the nervous system, astrocyte-like glia (ALG) have conserved functions to mammals and are essential for normal physiology and behaviours of the fly.In this study, we exploited the gene expression profile of single cells in Drosophila optic lobe to identify the genes with specific expression pattern in each cell type. Through a bioinformatical analysis of the data, a novel ALG-specific gene (here assigned as deathstar) was identified. Immunostaining of deathstar in the central nervous system (CNS) showed its presence in specific regions of Drosophila ventral nerve cord, which previously has been characterized as ALG cells. Consistent with the bioinformatical analysis, deathstar-related signals were overlapped with the signals of the previously-reported ALG marker, Eaat1, supporting its specific expression in ALG cells.At the physiological level, RNAi-mediated suppression of deathstar gene impeded the normal development of male flies without any effects on females. Cell type-specific expression of deathstar RNAi showed that deathstar gene affects locomotion behaviour and lifespan of D. melanogaster, in an ALG-specific manner.Taken together, we showed that bioinformatical analysis of a previously reported expression data of Drosophila optic lobe successfully predicted the ALG-specific expression pattern of deathstar gene. Moreover, it was consistent with the ALG-specific effects of this gene on locomotion and lifespan of D. melanogaster, in vivo.


2019 ◽  
Author(s):  
Hadi Najafi ◽  
Kyle Wong ◽  
Woo Jae Kim

Abstract Background: Drosophila melanogaster is a proper model organism for studying the development and function of the nervous system. The Drosophila nervous system consists of distinct cell types with significant homologies to various cell types of more advanced organisms, including human. Among all cell types of the nervous system, astrocyte-like glia (ALG) have conserved functions to mammals and are essential for normal physiology and behaviours of the fly.Results: In this study, we exploited the gene expression profile of single cells in Drosophila optic lobe to identify the genes with specific expression pattern in each cell type. Through a bioinformatical analysis of the data, a novel ALG-specific gene (here assigned as deathstar) was identified. Immunostaining of deathstar in the central nervous system (CNS) showed its presence in specific regions of Drosophila ventral nerve cord, which previously has been characterized as ALG cells. Consistent with the bioinformatical analysis, deathstar-related signals were overlapped with the signals of the previously-reported ALG marker, Eaat1, supporting its specific expression in ALG cells. At the physiological level, RNAi-mediated suppression of deathstar gene impeded the normal development of male flies without any effects on females. Cell type-specific expression of deathstar RNAi showed that deathstar gene affects locomotion behaviour and lifespan of D. melanogaster, in an ALG-specific manner.Conclusions: Taken together, we showed that bioinformatical analysis of a previously reported expression data of Drosophila optic lobe successfully predicted the ALG-specific expression pattern of deathstar gene. Moreover, it was consistent with the ALG-specific effects of this gene on locomotion and lifespan of D. melanogaster, in vivo.


2020 ◽  
Vol 119 (11) ◽  
pp. 2335-2348
Author(s):  
Kai Wang ◽  
Karla Kretschmannova ◽  
Rafael M. Prévide ◽  
Kosara Smiljanic ◽  
Qing Chen ◽  
...  

2018 ◽  
Author(s):  
Benoit P Nicolet ◽  
Sander Engels ◽  
Francesca Aglialoro ◽  
Emile van den Akker ◽  
Marieke von Lindern ◽  
...  

ABSTRACTHematopoietic stem cells differentiate into a broad range of specialized blood cells. This process is tightly regulated and depends on transcription factors, micro-RNAs, and long non-coding RNAs. Recently, also circular RNA (circRNA) were found to regulate cellular processes. Their expression pattern and their identity is however less well defined. Here, we provide the first comprehensive analysis of circRNA expression in human hematopoietic progenitors, and in differentiated lymphoid and myeloid cells. We here show that the expression of circRNA is cell-type specific, and increases upon maturation. circRNA splicing variants can also be cell-type specific. Furthermore, nucleated hematopoietic cells contain circRNA that have higher expression levels than the corresponding linear RNA. Enucleated blood cells, i.e. platelets and erythrocytes, were suggested to use RNA to maintain their function, respond to environmental factors or to transmit signals to other cells via microvesicles. Here we show that platelets and erythrocytes contain the highest number of circRNA of all hematopoietic cells, and that the type and numbers of circRNA changes during maturation. This cell-type specific expression pattern of circRNA in hematopoietic cells suggests a hithero unappreciated role in differentiation and cellular function.


2016 ◽  
Author(s):  
B. Ogan Mancarci ◽  
Lilah Toker ◽  
Shreejoy J Tripathy ◽  
Brenna Li ◽  
Brad Rocco ◽  
...  

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.


2021 ◽  
Vol 13 ◽  
Author(s):  
Simon J. O’Carroll ◽  
William H. Cook ◽  
Deborah Young

Different glial cell types are found throughout the central (CNS) and peripheral nervous system (PNS), where they have important functions. These cell types are also involved in nervous system pathology, playing roles in neurodegenerative disease and following trauma in the brain and spinal cord (astrocytes, microglia, oligodendrocytes), nerve degeneration and development of pain in peripheral nerves (Schwann cells, satellite cells), retinal diseases (Müller glia) and gut dysbiosis (enteric glia). These cell type have all been proposed as potential targets for treating these conditions. One approach to target these cell types is the use of gene therapy to modify gene expression. Adeno-associated virus (AAV) vectors have been shown to be safe and effective in targeting cells in the nervous system and have been used in a number of clinical trials. To date, a number of studies have tested the use of different AAV serotypes and cell-specific promoters to increase glial cell tropism and expression. However, true glial-cell specific targeting for a particular glial cell type remains elusive. This review provides an overview of research into developing glial specific gene therapy and discusses some of the issues that still need to be addressed to make glial cell gene therapy a clinical reality.


2013 ◽  
Vol 140 (5) ◽  
pp. 533-547 ◽  
Author(s):  
Christiane Kremser ◽  
Anna-Lena Klemm ◽  
Martina Uelft ◽  
Silke Imgrund ◽  
Christina Ginkel ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinting Guan ◽  
Yiping Lin ◽  
Yang Wang ◽  
Junchao Gao ◽  
Guoli Ji

Abstract Background Genome-wide association studies have identified genetic variants associated with the risk of brain-related diseases, such as neurological and psychiatric disorders, while the causal variants and the specific vulnerable cell types are often needed to be studied. Many disease-associated genes are expressed in multiple cell types of human brains, while the pathologic variants affect primarily specific cell types. We hypothesize a model in which what determines the manifestation of a disease in a cell type is the presence of disease module comprised of disease-associated genes, instead of individual genes. Therefore, it is essential to identify the presence/absence of disease gene modules in cells. Methods To characterize the cell type-specificity of brain-related diseases, we construct human brain cell type-specific gene interaction networks integrating human brain nucleus gene expression data with a referenced tissue-specific gene interaction network. Then from the cell type-specific gene interaction networks, we identify significant cell type-specific disease gene modules by performing statistical tests. Results Between neurons and glia cells, the constructed cell type-specific gene networks and their gene functions are distinct. Then we identify cell type-specific disease gene modules associated with autism spectrum disorder and find that different gene modules are formed and distinct gene functions may be dysregulated in different cells. We also study the similarity and dissimilarity in cell type-specific disease gene modules among autism spectrum disorder, schizophrenia and bipolar disorder. The functions of neurons-specific disease gene modules are associated with synapse for all three diseases, while those in glia cells are different. To facilitate the use of our method, we develop an R package, CtsDGM, for the identification of cell type-specific disease gene modules. Conclusions The results support our hypothesis that a disease manifests itself in a cell type through forming a statistically significant disease gene module. The identification of cell type-specific disease gene modules can promote the development of more targeted biomarkers and treatments for the disease. Our method can be applied for depicting the cell type heterogeneity of a given disease, and also for studying the similarity and dissimilarity between different disorders, providing new insights into the molecular mechanisms underlying the pathogenesis and progression of diseases.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jillian L. Lindblad ◽  
Meghana Tare ◽  
Alla Amcheslavsky ◽  
Alicia Shields ◽  
Andreas Bergmann

AbstractThe initiator caspase Dronc is the only CARD-domain containing caspase in Drosophila and is essential for apoptosis. Here, we report that homozygous dronc mutant adult animals are short-lived due to the presence of a poorly developed, defective and leaky intestine. Interestingly, this mutant phenotype can be significantly rescued by enteroblast-specific expression of dronc+ in dronc mutant animals, suggesting that proper Dronc function specifically in enteroblasts, one of four cell types in the intestine, is critical for normal development of the intestine. Furthermore, enteroblast-specific knockdown of dronc in adult intestines triggers hyperplasia and differentiation defects. These enteroblast-specific functions of Dronc do not require the apoptotic pathway and thus occur in a non-apoptotic manner. In summary, we demonstrate that an apoptotic initiator caspase has a very critical non-apoptotic function for normal development and for the control of the cell lineage in the adult midgut and therefore for proper physiology and homeostasis.


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