scholarly journals Regulation of Drosophila Hematopoiesis in Lymph Gland: From a Developmental Signaling Point of View

2020 ◽  
Vol 21 (15) ◽  
pp. 5246
Author(s):  
Wenwen Lan ◽  
Sumin Liu ◽  
Long Zhao ◽  
Ying Su
Keyword(s):  
Blood Cell ◽  
Signaling Pathways ◽  
Blood Cells ◽  
Cell Lineage ◽  
Lymph Gland ◽  
Point Of View ◽  
Hematopoietic System ◽  
Developmental Signaling ◽  
Progenitor Maintenance ◽  
Gland Development

The Drosophila hematopoietic system is becoming increasingly attractive for its simple blood cell lineage and its developmental and functional parallels with the vertebrate system. As the dedicated organ for Drosophila larval hematopoiesis, the lymph gland harbors both multipotent stem-like progenitor cells and differentiated blood cells. The balance between progenitor maintenance and differentiation in the lymph gland must be precisely and tightly controlled. Multiple developmental signaling pathways, such as Notch, Hedgehog, and Wnt/Wingless, have been demonstrated to regulate the hematopoietic processes in the lymph gland. Focusing on blood cell maintenance and differentiation, this article summarizes the functions of several classic developmental signaling pathways for lymph gland growth and patterning, highlighting the important roles of developmental signaling during lymph gland development as well as Drosophila larval hematopoiesis.

scholarly journals Pvr expression regulators in equilibrium signal control and maintenance of Drosophila blood progenitors

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Bama Charan Mondal ◽  
Jiwon Shim ◽  
Cory J Evans ◽  
Utpal Banerjee
Keyword(s):  
Drosophila Melanogaster ◽  
Blood Cells ◽  
Lymph Gland ◽  
Genetic Screen ◽  
Signal Control ◽  
Vegf Receptor ◽  
Interacting Protein ◽  
Hematopoietic Development ◽  
New Genes ◽  
Progenitor Maintenance

Blood progenitors within the lymph gland, a larval organ that supports hematopoiesis in Drosophila melanogaster, are maintained by integrating signals emanating from niche-like cells and those from differentiating blood cells. We term the signal from differentiating cells the ‘equilibrium signal’ in order to distinguish it from the ‘niche signal’. Earlier we showed that equilibrium signaling utilizes Pvr (the Drosophila PDGF/VEGF receptor), STAT92E, and adenosine deaminase-related growth factor A (ADGF-A) (<xref ref-type="bibr" rid="bib43">Mondal et al., 2011</xref>). Little is known about how this signal initiates during hematopoietic development. To identify new genes involved in lymph gland blood progenitor maintenance, particularly those involved in equilibrium signaling, we performed a genetic screen that identified bip1 (bric à brac interacting protein 1) and Nucleoporin 98 (Nup98) as additional regulators of the equilibrium signal. We show that the products of these genes along with the Bip1-interacting protein RpS8 (Ribosomal protein S8) are required for the proper expression of Pvr.

scholarly journals Headcase is a Repressor of Lamellocyte Fate in Drosophila melanogaster

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 173 ◽  
Author(s):  
Gergely I. B. Varga ◽  
Gábor Csordás ◽  
Gyöngyi Cinege ◽  
Ferenc Jankovics ◽  
Rita Sinka ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Differentiation ◽  
Blood Cell ◽  
Cell Fate ◽  
Blood Cells ◽  
Mutational Analysis ◽  
Genetic Interaction ◽  
Lymph Gland ◽  
Loss Of Function ◽  
Hematopoietic Stem

Due to the evolutionary conservation of the regulation of hematopoiesis, Drosophila provides an excellent model organism to study blood cell differentiation and hematopoietic stem cell (HSC) maintenance. The larvae of Drosophila melanogaster respond to immune induction with the production of special effector blood cells, the lamellocytes, which encapsulate and subsequently kill the invader. Lamellocytes differentiate as a result of a concerted action of all three hematopoietic compartments of the larva: the lymph gland, the circulating hemocytes, and the sessile tissue. Within the lymph gland, the communication of the functional zones, the maintenance of HSC fate, and the differentiation of effector blood cells are regulated by a complex network of signaling pathways. Applying gene conversion, mutational analysis, and a candidate based genetic interaction screen, we investigated the role of Headcase (Hdc), the homolog of the tumor suppressor HECA in the hematopoiesis of Drosophila. We found that naive loss-of-function hdc mutant larvae produce lamellocytes, showing that Hdc has a repressive role in effector blood cell differentiation. We demonstrate that hdc genetically interacts with the Hedgehog and the Decapentaplegic pathways in the hematopoietic niche of the lymph gland. By adding further details to the model of blood cell fate regulation in the lymph gland of the larva, our findings contribute to the better understanding of HSC maintenance.

scholarly journals Regulation of red blood cell filterability by Ca2+ influx and cAMP-mediated signaling pathways

1997 ◽  
Vol 273 (6) ◽  
pp. C1828-C1834 ◽  
Author(s):  
Tadahiro Oonishi ◽  
Kanako Sakashita ◽  
Nobuhiro Uyesaka
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Signaling Pathways ◽  
Mechanical Stress ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Camp Level ◽  
Membrane Properties ◽  
Cell Deformability ◽  
Red Blood Cell Deformability

To investigate the mechanism of the regulation of human red blood cell deformability, we examined the deformability under mechanical stress. Washed human red blood cells were rapidly injected through a fine needle, and their filterability was measured using a nickel mesh filter. The decrease in filterability showed a V-shaped curve depending on the extracellular Ca2+ concentration; the maximum decrease was achieved at ∼50 μM. The decreased filterability was accompanied by no change in cell morphology and cell volume, indicating that the decrease in filterability can be ascribed to alterations of the membrane properties. Ca2+entry blockers (nifedipine and felodipine) inhibited the impairment of filterability under mechanical stress. Prostaglandins E1 and E2, epinephrine, and pentoxifylline, which are thought to modulate the intracellular adenosine 3′,5′-cyclic monophosphate (cAMP) level of red blood cells, improved or worsened the impaired filterability according to their expected actions on the cAMP level of the cells. These results strongly suggest that the membrane properties regulating red blood cell deformability are affected by the signal transduction system, including Ca2+-dependent and cAMP-mediated signaling pathways.

scholarly journals Characterization of the Drosophila Adult Hematopoietic System Reveals a Rare Cell Population With Differentiation and Proliferation Potential

2021 ◽  
Vol 9 ◽  
Author(s):  
Manon Boulet ◽  
Yoan Renaud ◽  
François Lapraz ◽  
Billel Benmimoun ◽  
Laurence Vandel ◽  
...  
Keyword(s):  
Blood Cell ◽  
Blood Cells ◽  
Cell Types ◽  
Small Population ◽  
Differentiation Markers ◽  
Hematopoietic System ◽  
Small Set ◽  
Differentiation And Proliferation ◽  
Specialized Population

While many studies have described Drosophila embryonic and larval blood cells, the hematopoietic system of the imago remains poorly characterized and conflicting data have been published concerning adult hematopoiesis. Using a combination of blood cell markers, we show that the adult hematopoietic system is essentially composed of a few distinct mature blood cell types. In addition, our transcriptomics results indicate that adult and larval blood cells have both common and specific features and it appears that adult hemocytes reactivate many genes expressed in embryonic blood cells. Interestingly, we identify a small set of blood cells that does not express differentiation markers but rather maintains the expression of the progenitor marker domeMeso. Yet, we show that these cells are derived from the posterior signaling center, a specialized population of cells present in the larval lymph gland, rather than from larval blood cell progenitors, and that their maintenance depends on the EBF transcription factor Collier. Furthermore, while these cells are normally quiescent, we find that some of them can differentiate and proliferate in response to bacterial infection. In sum, our results indicate that adult flies harbor a small population of specialized cells with limited hematopoietic potential and further support the idea that no substantial hematopoiesis takes place during adulthood.

scholarly journals Characterization of the Drosophila adult hematopoietic system reveals a rare cell population with differentiation and proliferation potential.

2021 ◽  
Author(s):  
Manon Boulet ◽  
Yoan Renaud ◽  
Francois Lapraz ◽  
Billel Benmimoun ◽  
Laurence Vandel ◽  
...  
Keyword(s):  
Blood Cell ◽  
Blood Cells ◽  
Cell Types ◽  
Small Population ◽  
Differentiation Markers ◽  
Hematopoietic System ◽  
Small Set ◽  
Differentiation And Proliferation ◽  
Specialized Population

While many studies have described Drosophila embryonic and larval blood cells, the hematopoietic system of the imago remains poorly characterized and conflicting data have been published concerning adult hematopoiesis. Using a combination of blood cell markers, we show that the adult hematopoietic system is essentially composed of a few distinct mature blood cell types. In addition, our transcriptomics results indicate that adult and larval blood cells have both common and specific features and it appears that adult hemocytes reactivate many gene expressed in embryonic blood cells. Interestingly, we identify a small set of blood cells that do not express differentiation markers but maintain the progenitor marker domeMeso. Yet, we show that these cells are derived from the posterior signaling center, a specialized population of cells present in the larval lymph gland, rather than from larval blood cell progenitors, and that their maintenance depends on the EBF transcription factor Collier. Furthermore, while these cells are normally quiescent, we find that some of them can differentiate and proliferate in response to bacterial infection. In sum, our results indicate that adult flies harbor a small population of specialized cells with limited hematopoietic potential and further support the idea that no substantial hematopoiesis takes place during adulthood.

scholarly journals Rab5 and Rab11 maintain hematopoietic homeostasis by restricting multiple signaling pathways in Drosophila

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Shichao Yu ◽  
Fangzhou Luo ◽  
Li Hua Jin
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Membrane Trafficking ◽  
Genetic Model ◽  
Egfr Signaling ◽  
Blood Disorders ◽  
Hematopoietic System ◽  
Lymph Glands ◽  
Multiple Signaling ◽  
Progenitor Maintenance

The hematopoietic system of Drosophila is a powerful genetic model for studying hematopoiesis, and vesicle trafficking is important for signal transduction during various developmental processes; however, its interaction with hematopoiesis is currently largely unknown. In this article, we selected three endosome markers, Rab5, Rab7, and Rab11, that play a key role in membrane trafficking and determined whether they participate in hematopoiesis. Inhibiting Rab5 or Rab11 in hemocytes or the cortical zone (CZ) significantly induced cell overproliferation and lamellocyte formation in circulating hemocytes and lymph glands and disrupted blood cell progenitor maintenance. Lamellocyte formation involves the JNK, Toll, and Ras/EGFR signaling pathways. Notably, lamellocyte formation was also associated with JNK-dependent autophagy. In conclusion, we identified Rab5 and Rab11 as novel regulators of hematopoiesis, and our results advance the understanding of the mechanisms underlying the maintenance of hematopoietic homeostasis as well as the pathology of blood disorders such as leukemia.

scholarly journals 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

2021 ◽  
Vol 12 ◽  
Author(s):  
Ismaël Morin-Poulard ◽  
Yushun Tian ◽  
Nathalie Vanzo ◽  
Michèle Crozatier
Keyword(s):  
Blood Cell ◽  
Progenitor Cells ◽  
Blood Cells ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
Lymph Gland ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Stem ◽  
Hematopoietic Organ ◽  
Immune Stress

In adult mammals, blood cells are formed from hematopoietic stem progenitor cells, which are controlled by a complex cellular microenvironment called “niche”. Drosophila melanogaster is a powerful model organism to decipher the mechanisms controlling hematopoiesis, due both to its limited number of blood cell lineages and to the conservation of genes and signaling pathways throughout bilaterian evolution. Insect blood cells or hemocytes are similar to the mammalian myeloid lineage that ensures innate immunity functions. Like in vertebrates, two waves of hematopoiesis occur in Drosophila. The first wave takes place during embryogenesis. The second wave occurs at larval stages, where two distinct hematopoietic sites are identified: subcuticular hematopoietic pockets and a specialized hematopoietic organ called the lymph gland. In both sites, hematopoiesis is regulated by distinct niches. In hematopoietic pockets, sensory neurons of the peripheral nervous system provide a microenvironment that promotes embryonic hemocyte expansion and differentiation. In the lymph gland blood cells are produced from hematopoietic progenitors. A small cluster of cells called Posterior Signaling Centre (PSC) and the vascular system, along which the lymph gland develops, act collectively as a niche, under homeostatic conditions, to control the balance between maintenance and differentiation of lymph gland progenitors. In response to an immune stress such as wasp parasitism, lymph gland hematopoiesis is drastically modified and shifts towards emergency hematopoiesis, leading to increased progenitor proliferation and their differentiation into lamellocyte, a specific blood cell type which will neutralize the parasite. The PSC is essential to control this emergency response. In this review, we summarize Drosophila cellular and molecular mechanisms involved in the communication between the niche and hematopoietic progenitors, both under homeostatic and stress conditions. Finally, we discuss similarities between mechanisms by which niches regulate hematopoietic stem/progenitor cells in Drosophila and mammals.

The Role of the Distal Erythropoietin Receptor in Iron Deficiency Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1312-1312
Author(s):  
Grant C. Bullock ◽  
Lorrie L. Delehanty ◽  
Anne-Laure A Talbot ◽  
Chante Richardson ◽  
Adam Goldfarb
Keyword(s):  
Iron Deficiency ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Signaling Pathways ◽  
Red Blood Cell ◽  
Blood Cells ◽  
Deficiency Anemia ◽  
Red Cell ◽  
Iron Restriction

Abstract Abstract 1312 Anemia affects the quality of life and the life expectancy of millions of people in the U.S. Many patients are either intolerant or unresponsive to available treatments, so alternative strategies are needed. Red blood cell production requires the action of erythropoietin (Epo) on red blood cell precursors in the bone marrow. Iron restriction results in loss of Epo-responsiveness and anemia, despite increased serum Epo levels. Iron infusion restores Epo-responsiveness suggesting that iron dominantly regulates Epo-receptor (EpoR) signaling. Understanding how iron restriction regulates EpoR signaling pathways has major clinical significance. Agonists could offer an iron-free approach that enhances the response to Epo in anemia due to iron deficiency or chronic diseases. In addition, antagonists could be used to treat polycythemia vera or other myeloproliferative disorders. We have discovered that the aconitases, multifunctional iron-sulfur cluster proteins that convert citrate into isocitrate are key in connecting iron to Epo-signaling in early erythroid progenitors (GC Bullock, et. al. Blood 2010;116:97). We also discovered that isocitrate, the downstream product of aconitase, can enhance the effectiveness of Epo during iron deficiency in vitro and in vivo in mice with IDA. These observations suggest that isocitrate or derivatives of isocitrate that synergize with erythropoiesis stimulating agents (ESAs) have important therapeutic application in the treatment of anemia. Deletion of EpoR in mice is incompatible with life, however mice and humans that express truncated EpoR show increased production of red blood cells. These observations suggest that the distal cytoplasmic domain of the EpoR inhibits production of red cells and may play a critical role in iron deficiency anemia. EpoR mutant mice lacking the distal half of the cytoplasmic domain of the EpoR (EpoR-H mice) and mice with the same EpoR truncation mutation plus an additional mutation of tyrosine 343 (EpoR-HM mice) show near normal levels of steady state erythropoiesis. To determine the role of the distal domain in erythroid suppression during iron deficiency, EpoR-H, EpoR-HM and EpoR-wildtype mice were fed a low iron diet and compared by weekly CBCs and flow cytometry. EpoR-H mutant mice continue to efficiently produce red blood cells during iron deficiency. And this occurs despite a decrease in hemoglobin. EpoR-HM mice produce fewer rbcs than EpoR-H mice, however rbc production by EpoR-HM mice resists the suppressive effects of iron restriction. Similar experiments also suggest that the distal EpoR is necessary for the isocitrate-mediated enhancement of Epo-driven erythropoiesis. In addition to aconitase/isocitrate and the distal EpoR other candidate key signaling components of this Epo-dependent, iron-responsive pathway have been identified in our recent preliminary experiments. These components include specific protein kinase C (PKC) isozymes, AKT1 and ERK1/2. These findings support a new model of iron sensing by aconitase/isocitrate that alters EpoR signaling to decrease red blood cell production and conserve iron when supplies are low. This model fits better than older “heme-deficiency” models because disorders in heme synthesis block red cell differentiation at a later stage. This model also has potential to explain changes seen in other tissues during chronic iron deficiency. Nutritional iron restriction may have unmasked a new role for the distal EpoR in red cell development and implicated new iron-responsive Epo signaling pathways that can be used to develop new therapeutic agonists and antagonists of Epo. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Differential activation of JAK-STAT signaling in blood cell progenitors reveals functional compartmentalization of the Drosophila lymph gland

2020 ◽  
Author(s):  
Diana Rodrigues ◽  
Yoan Renaud ◽  
K. VijayRaghavan ◽  
Lucas Waltzer ◽  
Maneesha S. Inamdar
Keyword(s):  
Blood Cells ◽  
Molecular Genetic ◽  
Lymph Gland ◽  
Dependent Manner ◽  
Immune Challenge ◽  
Depth Analysis ◽  
Stat Signaling ◽  
Stem And Progenitor Cells ◽  
Progenitor Maintenance

AbstractBlood cells arise from diverse pools of stem and progenitor cells. Understanding progenitor heterogeneity is a major challenge. The Drosophila larval lymph gland is a well-studied model to understand blood progenitor maintenance and recapitulates several aspects of vertebrate hematopoiesis. However in-depth analysis has focused on progenitors located in lymph gland anterior lobes (AP), ignoring the progenitors from the posterior lobes (PP). Using in situ expression mapping and transcriptome analysis we reveal PP heterogeneity and identify molecular-genetic tools to study this abundant progenitor population. Functional analysis shows that PP resist differentiation upon immune challenge, in a JAK-STAT-dependent manner. Upon wasp parasitism, AP downregulate JAK-STAT signaling and form lamellocytes. In contrast, we show that PP activate STAT92E and remain undifferentiated. Stat92E knockdown in PP or genetically reducing JAK-STAT signaling permits PP lamellocyte differentiation. We discuss how heterogeneity and compartmentalization allow functional segregation in response to systemic cues and could be widely applicable.HighlightsWe provide an in situ and transcriptome map of larval blood progenitors Posterior lymph gland progenitors are refractory to immune challenge STAT activation after wasp parasitism maintains posterior progenitors

DMSP – Database for Modeling Signaling Pathways

2008 ◽  
Vol 47 (02) ◽  
pp. 104-148
Author(s):  
M. Breit ◽  
B. Pfeifer ◽  
C. Baumgartner ◽  
R. Modre-Osprian ◽  
B. Tilg ◽  
...  
Keyword(s):  
Knowledge Base ◽  
Signaling Pathways ◽  
Protein Interaction ◽  
Initial Step ◽  
Point Of View ◽  
Biological Knowledge ◽  
Literature Study ◽  
Online Databases ◽  
Qualitative Level ◽  
Pathway Models

Summary Objectives: Presently, the protein interaction information concerning different signaling pathways is available in a qualitative manner in different online protein interaction databases. The challenge here is to derive a quantitative way of modeling signaling pathways from qualitative way of modeling signaling pathways from a qualitative level. To address this issue we developed a database that includes mathematical modeling knowledge and biological knowledge about different signaling pathways. Methods: The database is part of an integrative environment that includes environments for pathway design, visualization, simulation and a knowledge base that combines biological and modeling information concerning pathways. The system is designed as a client-server architecture. It contains a pathway designing environment and a simulation environment as upper layers with a relational knowledge base as the underlying layer. Results: DMSP – Database for Modeling Signaling Pathways incorporates biological datasets from online databases like BIND, DIP, PIP, and SPiD. The modeling knowledge that has been incorporated is based on a literature study. Pathway models can be designed, visualized and simulated based on the knowledge stored in the DMSP. The user can download the whole dataset and build pathway models using the knowledge stored in our database. As an example, the TNF? pathway model was implemented and tested using this approach. Conclusion: DMSP is an initial step towards the aim of combining modeling and biological knowledge concerning signaling pathways. It helps in understanding pathways in a qualitative manner from a qualitative level. Simulation results enable the interpretation of a biological system from a quantitative and systemtheoretic point of view.

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