Interaction between Differentiating Cell- and Niche-Derived Signals in Hematopoietic Progenitor Maintenance

Abstract

Summary Maintenance of a hematopoietic progenitor population requires extensive interaction with cells within a microenvironment or niche. In the Drosophila hematopoietic organ, niche-derived Hedgehog signaling maintains the progenitor population. Here we show that the hematopoietic progenitors also require a signal mediated by Adenosine deaminase growth factor A (Adgf-A) arising from differentiating cells that regulates extracellular levels of adenosine. The adenosine signal opposes the effects of Hedgehog signaling within the hematopoietic progenitor cells and the magnitude of the adenosine signal is kept in check by the level of Adgf-A secreted from differentiating cells. Our findings reveal signals arising from differentiating cells that are required for maintaining progenitor cell quiescence, and that function with the niche-derived signal in maintaining the progenitor state. Similar homeostatic mechanisms are likely to be utilized in other systems that maintain relatively large numbers of progenitors that are not all in direct contact with the cells of the niche.

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

“…However, Pvr overexpression did restore the ARF1-depleted niche loss, indicating that an alternate mechanism for STAT activation may operate from the CZ or circulating hemocytes. The control of AdgfA activity by Stat has been demonstrated (25). We have shown that Stat92e activation is mediated by Asrij (7).…”

“…Prohemocyte maintenance is achieved by a balanced response to signals from the niche and from differentiated cells of the CZ (25). Because ARF1 depletion in the CZ affects niche maintenance non-cell autonomously and also results in induction of differentiation, we studied the effect of modulating ARF1 levels on the Pvf/Pvr/Stat/ AdgfA axis that signals from the niche to the CZ and back to MZ prohemocytes (25). Because Asrij has a conserved role in endosomally regulating JAK/STAT signaling to maintain stem cell potency in Drosophila hematopoiesis, we investigated whether ARF1 is involved in this axis.…”

Reactive Oxygen Species Affect Transglutaminase Activity and Regulate Hematopoiesis in a Crustacean

“…In addition, Trol regulates PDGF signaling in plasmatocytes (12). PDGF-like factors and their receptors, PDGF/VEGF receptors, are involved in hemocyte production in the Drosophila embryo (13)(14)(15). The interaction between Trol and the PDGF/VEGF receptor signaling pathway participates in hemocyte homeostasis in Drosophila (11,12).…”

Haematopoietic progenitor maintenance by EBF/Collier: beyond the Niche

“…3 Also, differentiated blood cells feedback on prohemocytes to keep them undifferentiated. 6 In addition, a compact extracellular matrix (ECM) is observed around the Medullary Zone/prohemocytes and modulating ECM composition affects prohemocyte maintenance. 7 Furthermore, one could speculate that cells of the cardiac tube that are lining the LG participate in prohemocyte maintenance.…”