The Drosophila lymph gland is an ideal model for studying hematopoiesis

Yu, Shichao; Luo, Fangzhou; Jin, Li

doi:10.1016/j.dci.2017.11.017

Cited by 29 publications

(34 citation statements)

References 99 publications

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“…The blood progenitors of late larval lymph gland are arrested in G2-M phase of cell cycle ( Sharma et al, 2019 ), have high levels of ROS ( Owusu-Ansah and Banerjee, 2009 ), lack differentiation markers, are multipotent ( Jung et al, 2005 ) and are maintained by the hematopoietic niche/posterior signaling center, PSC ( Krzemień et al, 2007 ; Lebestky et al, 2003 ; Mandal et al, 2007 ). The primary lobe has been extensively used to understand intercellular communication relevant to progenitor maintenance ( Gao et al, 2013 ; Giordani et al, 2016 ; Gold and Brückner, 2014 ; Hao and Jin, 2017 ; Krzemień et al, 2007 ; Krzemien et al, 2010 ; Lebestky et al, 2003 ; Mandal et al, 2007 ; Mondal et al, 2011 ; Morin-Poulard et al, 2016 ; Sinenko et al, 2009 ; Small et al, 2014 ; Yu et al, 2018 ). Although these studies have contributed significantly toward our understanding of cellular signaling relevant for progenitor homeostasis, the role of cellular metabolism in regulating the state and fate of blood progenitors remains to be addressed.…”

Section: Introductionmentioning

confidence: 99%

Fatty acid β-oxidation is required for the differentiation of larval hematopoietic progenitors in Drosophila

Tiwari

Toshniwal

Mandal

et al. 2020

eLife

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Cell-intrinsic and extrinsic signals regulate the state and fate of stem and progenitor cells. Recent advances in metabolomics illustrate that various metabolic pathways are also important in regulating stem cell fate. However, our understanding of the metabolic control of the state and fate of progenitor cells is in its infancy. Using Drosophila hematopoietic organ: lymph gland, we demonstrate that Fatty Acid Oxidation (FAO) is essential for the differentiation of blood cell progenitors. In the absence of FAO, the progenitors are unable to differentiate and exhibit altered histone acetylation. Interestingly, acetate supplementation rescues both histone acetylation and the differentiation defects. We further show that the CPT1/whd (withered), the rate-limiting enzyme of FAO, is transcriptionally regulated by Jun-Kinase (JNK), which has been previously implicated in progenitor differentiation. Our study thus reveals how the cellular signaling machinery integrates with the metabolic cue to facilitate the differentiation program.

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Section: Introductionmentioning

confidence: 99%

Fatty acid β-oxidation is required for the differentiation of larval hematopoietic progenitors in Drosophila

Tiwari

Toshniwal

Mandal

et al. 2020

eLife

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“…Starvation or loss of insulin signaling results in the differentiation of progenitors and activation of inflammatory responses, recapitulating a diabetic-like condition ( 18 ). Nutrient-rich conditions ( 19 ) or any change in the physiological state of the developing larvae ( 3 ) have been shown to alter immune cell numbers as well. As immune cells undergo functional maturation, the macrophage-like plasmatocytes perform lipid-scavenging functions and exert systemic control on glucose homeostasis and survival on lipid-rich diet ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

Immune Control of Animal Growth in Homeostasis and Nutritional Stress in Drosophila

et al. 2020

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A large body of research implicates the brain and fat body (liver equivalent) as central players in coordinating growth and nutritional homeostasis in multicellular animals. In this regard, an underlying connection between immune cells and growth is also evident, although mechanistic understanding of this cross-talk is scarce. Here, we explore the importance of innate immune cells in animal growth during homeostasis and in conditions of nutrient stress. We report that Drosophila larvae lacking blood cells eclose as small adults and show signs of insulin insensitivity. Moreover, when exposed to dietary stress of a high-sucrose diet (HSD), these animals are further growth retarded than normally seen in regular animals raised on HSD. In contrast, larvae carrying increased number of activated macrophage-like plasmatocytes show no defects in adult growth when raised on HSD and grow to sizes almost comparable with that seen with regular diet. These observations imply a central role for immune cell activity in growth control. Mechanistically, our findings reveal a surprising influence of immune cells on balancing fat body inflammation and insulin signaling under conditions of homeostasis and nutrient overload as a means to coordinate systemic metabolism and adult growth. This work integrates both the cellular and humoral arm of the innate immune system in organismal growth homeostasis, the implications of which may be broadly conserved across mammalian systems as well.

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“…In the lymph gland, prohemocyte state and effector hemocyte differentiation are controlled by a complex signaling network. Major components of this network that contribute to hemocyte fate choice are the Hedgehog (Hh), the Decapentaplegic (Dpp), and the JAK/STAT signaling pathways [11,32,38,39,40].…”

Section: Introductionmentioning

confidence: 99%

Headcase is a Repressor of Lamellocyte Fate in Drosophila melanogaster

Varga

Csordás

Cinege

et al. 2019

Genes

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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.

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The Drosophila lymph gland is an ideal model for studying hematopoiesis

Cited by 29 publications

References 99 publications

Fatty acid β-oxidation is required for the differentiation of larval hematopoietic progenitors in Drosophila

Fatty acid β-oxidation is required for the differentiation of larval hematopoietic progenitors in Drosophila

Immune Control of Animal Growth in Homeostasis and Nutritional Stress in Drosophila

Headcase is a Repressor of Lamellocyte Fate in Drosophila melanogaster

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