Direct sensing of systemic and nutritional signals by haematopoietic progenitors in Drosophila

Abstract

The Drosophila lymph gland is a hematopoietic organ in which progenitor cells, which are most akin to the common myeloid progenitor or CMP in mammals, proliferate and differentiate into three types of mature cells – plasmatocytes, crystal cells and lamellocytes – the functions of which are reminiscent of mammalian myeloid cells1. During the first and early second instars of larval development, the lymph gland contains only progenitors, whereas in the third instar, a medial region of the primary lobe of the lymph gland called the medullary zone (MZ) contains these progenitors2, while maturing blood cells are found juxtaposed in a peripheral region designated the cortical zone (CZ)2. A third group of cells referred to as the posterior signaling center (PSC) functions as a hematopoietic niche3,4. Similar to mammalian myeloid cells, Drosophila blood cells respond to multiple stresses including hypoxia, infection, and oxidative stress5–7. However, how systemic signals are sensed by myeloid progenitors to regulate cell fate determination has not been well described. Here, we show that the hematopoietic progenitors of Drosophila are direct targets of systemic (insulin) and nutritional (essential amino acid) signals, and that these systemic signals maintain the progenitors by promoting Wingless (WNT in mammals) signaling. We expect that this study will promote investigation of such possible direct signal sensing mechanisms by mammalian myeloid progenitors.

ARF1–GTP regulates Asrij to provide endocytic control of Drosophila blood cell homeostasis

“…Thus, ARF1 negatively regulates differentiation and we found that this is due to its effect on the hematopoietic stem cell niche (PSC). Recent studies showed that lymph gland hematopoiesis is regulated by autonomous as well as systemic factors (26,27). Our analysis shows an essential resident role for ARF1 in the niche as well as for communication from the nonlymph-gland hemocytes.…”

Stem cell metabolism in tissue development and aging

“…Perhaps more strikingly, rapamycin treatment late in adulthood can extend organismal longevity in mice (Harrison et al, 2009). These mechanisms appear to be well-conserved in Drosophila too, as insulin-PI3K signaling also regulates the proliferative capacity of Drosophila hematopoietic progenitors (Shim et al, 2012), neuroblasts (Chell and Brand, 2010;Sousa-Nunes et al, 2011), intestinal stem cells (ISCs) (Biteau et al, 2010;Choi et al, 2011;O'Brien et al, 2011) and germline stem cells (GSCs) (12) stem cell metabolism, by acting as nutrient sensors that modulate regenerative capacity during aging (Fig. 5C).…”

Nutritional regulation of stem and progenitor cells in Drosophila

“…Nutritional deprivation directly impinges on the maintenance of blood progenitors in the lymph gland and causes the expansion of mature blood cells (Benmimoun et al, 2012;Dragojlovic-Munther and Martinez-Agosto, 2012;Shim et al, 2012;Tokusumi et al, 2012). Twenty-four hour starvation of third instar larvae dramatically increases the differentiation of mature blood cells and concomitantly decreases blood progenitors (Benmimoun et al, 2012;Dragojlovic-Munther and Martinez-Agosto, 2012;Shim et al, 2012).…”