Drosophila Blood Cell Differentiation Group

The immune system is the main defense barrier that protects organisms against parasites, pathogens and harmful effects. The fruit fly Drosophila melanogaster has been used to study immunity and blood cell differentiation for the past 60 years. Although, according to our recent knowledge, Drosophila lacks an adaptive immunity, the functions of its immune cells (the hemocytes), such as phagocytosis, encapsulation and coagulation are similar to those of vertebrate myeloid cells. The signaling pathways, as well as the transcription and epigenetic factors that regulate blood cell differentiation are highly conserved. Similarly to vertebrate blood cells, hemocytes differentiate in spatially separated hematopoietic compartments in multiple waves. Therefore, Drosophila is an ideal model organism to study the regulation of stem cell function in the hematopoietic niche, as well as tumor formation caused by the misregulation of blood cell fate.

1. Transdifferentiation of Drosophila blood cells

Transdifferentiation is a conversion of an already differentiated cell type into another cell type without the involvement of stem cells. Our transgenic cell lineage tracing experiments revealed that the phagocytic plasmatocytes of the larva are plastic cells that are capable of differentiating into capsule forming lamellocytes upon immune induction. During this conversion, plasmatocytes undergo dramatic morphological alterations and gene expression changes. To study transdifferentiation, we set up an ex vivo hemocyte culturing and differentiation method, which enables time-lapse microscopy of blood cells and the detailed, high-throughput analysis of morphological changes with machine learning. Our aim is to correlate hemocyte morphology with transcriptomic changes to better understand the transdifferentiation process.

2. The role of Headcase in the regulation of hemocyte progenitor maintenance

Headcase, the Drosophila homolog of the human tumor suppressor HECA, was shown to regulate hemocyte fate in the lymph gland, one of the hemocyte compartments of the larva. According to our previous results, Headcase exerts its function in the hematopoietic niche of the lymph gland, and regulates hemocyte progenitor maintenance via modulation of Hedgehog, Decapentaplegic and JAK/STAT signaling. Our aim is to identify the functional domains and interacting partners of Headcase to better understand its role in the regulation of hemocyte differentiation.

References:

Csordás, G., Gábor, E., Honti, V., 2020. There and back again: The mechanisms of differentiation and transdifferentiation in Drosophila blood cells. Dev. Biol. (submitted)

Varga, G.I.B., Csordás, G., Cinege, G., Jankovics, F., Sinka, R., Kurucz, É., Andó, I., Honti, V., 2019. Headcase is a Repressor of Lamellocyte Fate in Drosophila melanogaster. Genes 10. https://doi.org/10.3390/genes10030173

Honti, V., Csordás, G., Kurucz, É., Márkus, R., Andó, I., 2014. The cell-mediated immunity of Drosophila melanogaster: hemocyte lineages, immune compartments, microanatomy and regulation. Dev. Comp. Immunol. 42, 47–56. https://doi.org/10.1016/j.dci.2013.06.005

Honti, V., Csordás, G., Márkus, R., Kurucz, E., Jankovics, F., Andó, I., 2010. Cell lineage tracing reveals the plasticity of the hemocyte lineages and of the hematopoietic compartments in Drosophila melanogaster. Mol. Immunol. 47, 1997–2004. https://doi.org/10.1016/j.molimm.2010.04.017

Honti, V., Kurucz, E., Csordás, G., Laurinyecz, B., Márkus, R., Andó, I., 2009. In vivo detection of lamellocytes in Drosophila melanogaster. Immunol. Lett. 126, 83–84. https://doi.org/10.1016/j.imlet.2009.08.004