Biology subjects

Pavlidaki, A.

Publications and source records attributed to Pavlidaki, A..

3 recordsLinked to original sources

bioRxiv2022

Novel cell- and stage-specific transcriptional signatures defining Drosophila neurons, glia and hemocytes

Cell types can be now defined at unprecedented resolution using high throughput assays. We analyzed the transcriptional signatures of Drosophila neurons, glia and hemocytes, as examples of cell types that are related by position (glia/neurons) or function (glia/hemocytes) or that are unrelated (neurons/hemocytes). The most related cells display the highest similarity level (neurons and glia), the least related ones, the lowest (neurons and hemocytes), however, cells can show plastic features. Glia are much more similar to neurons than to hemocytes in the embryo, but are equally similar to the two cell types in the larva, when hemocytes acquire more immune functions. Larval glia and hemocytes display common as well as specific immune features, such as the glia-specific NimA receptor, in agreement with the different environment faced by each cell types. Surprisingly, time represents a key identity parameter, as neurons, hemocytes and glia group more significantly by the stage than by the cell type and larval cells show upregulation of genes involved in chromatin organization and in DNA repair. This latter group of genes is linked to changes in gene expression levels and chromatin organization, revealing a function of these genes beyond DNA repair. Finally, the metabolic profiles reveal cell type-specific signatures and an overall shift from an embryonic, anabolic state to a larval, catabolic state.

developmental biology↗

bioRxiv2022

Gcm: a novel anti-inflammatory transcriptional cascade conserved from flies to humans

Innate immunity is an ancestral process that can induce pro- and anti-inflammatory states. A major challenge is to characterise the transcriptional cascades that modulate the response to chronic and acute inflammatory challenges. The Drosophila melanogaster Gcm transcription factor represents an interesting candidate for its potential anti-inflammatory role. Here we explore its evolutionary conservation and its mode of action. We found that the murine ortholog Gcm2 (mGcm2) is expressed upon aging, which is considered as a state of chronic inflammation. mGcm2 is found in a subpopulation of microglia, the innate immune cells of the central nervous system (CNS). Its expression is also induced by a lyso-phosphatidylcholine (LPC)-induced CNS demyelination (acute inflammation) and mGcm2 conditional knock out mice show an increased inflammatory phenotype upon aging or LPC injection. In agreement with the role of this transcriptional cascade in inflammation, the human ortholog hGCM2 is expressed in active demyelinating lesions of Multiple Sclerosis (MS) patients. Finally, Drosophila gcm expression is induced upon aging as well as during an acute inflammatory response and its overexpression decreases the inflammatory phenotype. Altogether, our data show that the inducible Gcm pathway is highly conserved from flies up to humans and represents a potential therapeutic anti-inflammatory target in the control of the inflammatory response.

neuroscience↗

bioRxiv2019

Temporal specificity and heterogeneity of the fly immune cells' transcriptional landscape

Immune cells provide defense against the non-self, however recent data suggest roles well beyond innate immunity, in processes as diverse as development, metabolism and tumor progression. Nevertheless, the heterogeneity of these cells remains an open question. Using bulk RNA sequencing we find that the Drosophila immune cells (hemocytes) display distinct features in the embryo, a closed and rapidly developing system, compared to the larva, which is exposed to environmental and metabolic challenges. Through single cell RNA sequencing we identify fourteen hemocyte clusters present in unchallenged larvae and associated with distinct cellular processes e.g. proliferation, phagocytosis, metabolic homeostasis and humoral response. Finally, we characterize the changes occurring in the hemocyte clusters upon wasp infestation that triggers the differentiation of a novel cell type, the lamellocyte. This first molecular atlas provides precious insights and paves the way to study the biology of the Drosophila immune cells in physiological and pathological conditions.

developmental biology↗