Team

Hematopoiesis and immunity in Drosophila

Presentation

In the adult mammalian bone marrow, the renewal of blood cells is ensured by stem/progenitor cells through their regulation via signals coming from different surrounding cell types called microenvironment or “niche”. Given the complexity of the mechanisms involved and the high conservation of regulatory networks among insects and vertebrates, the Drosophila hematopoietic organ, the lymph gland (LG), has become an important model to study hematopoiesis. The LG lies along the cardiac tube which is the vascular system. A small cluster of LG cells called the Posterior Signaling Center (PSC), together with cardiac cells, which is the vascular system, act as niches to control hematopoiesis under normal conditions. In response to an immune stress, LG hematopoiesis shifts towards stress hematopoiesis. While our knowledge of HSPC/niche cell communication under normal conditions progresses, the processes that occur following an immune stress remain more elusive. The goal of our project is to determine how information from multiple cell types/sources is coordinated and integrated to regulate LG hematopoiesis under physiological conditions and in response to immune stress.

Project

We observed that a somatic muscle (AM1) and CNS neurons are in proximity to the LG, revealing a complex tissular environment around the LG. We established the transcriptional profiles of LG cells and associated tissues at single cell resolution, prior to and following parasitism. By combining functional analyses of candidate genes (our “scRNAseq”), confocal, expansion and electron microscopy, we plan to unravel how diverse cellular microenvironments (PSC, cardiac cells, AM1 and neurons) organize around and communicate with the LG in order to regulate hematopoiesis.

Team members

– Tian Y, Morin-Poulard I, Liu X., Vanzo N. and Crozatier M*. (2023). A mechanosensitive vascular niche for Drosophila hematopoiesis. PNAS 120 (18) e2217862120, https://doi.org/10.1073/pnas.2217862120

– Morin-Poulard* I., Destalminil-Letourneau M., Bataille L., Frendo J.L., Lebreton G., Vanzo N. and Crozatier M.* (2022). Identification of bi-potential blood cell/nephrocyte progenitors in Drosophila: another route for generating blood progenitors. Front. Cell Dev. Biol., 14 February 2022, doi:10.3389/fcell.2022.834720

Moussalem D., Augé B., Di Stefano L., Osman D., Gobert V. and Haenlin M.*(2022). Two Isoforms of serpent Containing Either One or Two GATA Zinc Fingers Provide Functional Diversity During Drosophila Development. Front. Cell Dev. Biol., 01 February 2022 | https://doi.org/10.3389/fcell.2021.795680

– Morin-Poulard I, Tian Y, Vanzo N, Crozatier M.* (2021). Drosophila as a Model to Study Cellular Communication Between the Hematopoietic Niche and Blood Progenitors Under Homeostatic Conditions and in Response to an Immune Stress. Front Immunol Aug 16;12:719349. doi: 10.3389/fimmu.2021.719349. eCollection 2021. PMID: 34484226 (review)

– Destalminil-Letourneau M, Morin-Poulard I, Tian Y, Vanzo N, Crozatier M.* (2021). The vascular niche controls Drosophila hematopoiesis via fibroblast growth factor signaling. Elife. Jan 4;10:e64672. doi: 10.7554/eLife.64672.PMID: 33395389

– Louradour I, Sharma A, Morin-Poulard I, Letourneau M, Vincent A, Crozatier M*, Vanzo N*. (2017). Reactive oxygen species-dependent Toll/NF-κB activation in the Drosophila hematopoietic niche confers resistance to wasp parasitism. Elife. Nov 1;6:e25496. doi: 10.7554/eLife.25496. PMID: 29091025

– Miller M, Chen A, Gobert V, Augé B, Beau M, Burlet-Schiltz O, Haenlin M, Waltzer L. (2017). Control of RUNX-induced repression of Notch signaling by MLF and its partner DnaJ-1 during Drosophila hematopoiesis. PLoS Genet. Jul 25;13(7):e1006932. doi: 10.1371/journal.pgen.1006932. eCollection 2017 Jul. PMID: 28742844

– Morin-Poulard I, Sharma A, Louradour I, Vanzo N, Vincent A, Crozatier M.* (2016). Vascular control of the Drosophila haematopoietic microenvironment by Slit/Robo signaling. Nat Commun. May 19;7:11634. doi: 10.1038/ncomms11634.PMID: 27193394

– Oyallon J, Vanzo N, Krzemień J, Morin-Poulard I, Vincent A, Crozatier M.* (2016). Two Independent Functions of Collier/Early B Cell Factor in the Control of Drosophila Blood Cell Homeostasis. PLoS One. Feb 11;11(2):e0148978. doi: 10.1371/journal.pone.0148978. eCollection 2016. PMID: 26866694

– Benmimoun B, Polesello C, Haenlin M, Waltzer L (2015). The EBF transcription factor Collier directly promotes Drosophila blood cell progenitor maintenance independently of the niche. Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):9052-7. doi: 10.1073/pnas.1423967112.

– Pennetier D., Oyallon J., Morin-Poulard I., Dejean S., Vincent A. and Crozatier. M* (2012). Size control of the Drosophila hematopoietic niche by bone morphogenetic protein signaling reveals parallels with mammals. PNAS, 109 (9): 3389-3394.

– Makki R., Meister M., Pennetier D., Ubeda J.M., Braun A., Daburon V., Krzemien J., Bourbon H.M., Zhour R., Vincent A. and Crozatier M.*(2010). A short receptor down-regulates JAK/STAT signalling to control the Drosophila cellular immune response. PLoS Biology,8:8, e1000441.

– Krzemien J., Dubois L., Makki R., Meister M., Vincent A. and Crozatier M* (2007). Control of blood homeostasis in Drosophila larvae by the Posterior Signaling Center. (Nature , 446 : 325-328)

Crozatier M., Ubeda J.M., Vincent A. and Meister M. (2004). Cellular Immune Response to parasitization in Drosophila requires the EBF orthologue Collier. PloS Biology 2 :1107-1113.

Funding

Affiliation