DROSOHEMATO

In the adult mammalian bone marrow, the constant renewal of blood cells is ensured by hematopoietic stem/progenitor cells through their regulation via signals coming from different surrounding cell types called microenvironment or “niche”. Given the complexity of the cellular and molecular 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, act as niches to control hematopoiesis under normal conditions. In response to an immune stress, such as wasp parasitism, LG hematopoiesis shifts towards stress hematopoiesis. Recently, we observed that a somatic muscle (AM1) and CNS neurons are in proximity to the LG, revealing a complex tissular cellular environment around the LG. Furthermore, our preliminary data indicate that in addition to the PSC, cardiac cells, AM1 and neurons are involved in regulating LG stress hematopoiesis. Recently, we established the transcriptional profiles of LG cells and associated tissues at single cell resolution, prior to and following parasitism. This revealed a high level of heterogeneity among both hematopoietic progenitors and PSC cells, raising the possibility that specific subsets of PSC cells are dedicated to the control of specific subsets of progenitors. By combining complementary approaches such as functional analyses of candidate genes (our "scRNAseq"), functional RNAi screens, genome editing, confocal, expansion and electron microscopy, we plan to unravel at the cellular and molecular levels how diverse cellular microenvironments (PSC, cardiac cells, AM1 and neurons) organize around and communicate with the LG in order to regulate LG stress hematopoiesis.