Context-specific functions of Notch in <i>Drosophila</i> blood cell progenitors

Blanco-Obregon, DM; Katz, M.J.; Durrieu, L.; Gándara, Lautaro; Wappner, Pablo

doi:10.1101/682658

Cited by 5 publications

(8 citation statements)

References 49 publications

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“…3C’). This pattern of activity was reminiscent of the positioning of the intermediate or transitioning progenitors (Blanco-Obregon et al, 2020) and the sensor expression analysis highlighted dopamine signalling at this interface.…”

Section: Resultsmentioning

confidence: 81%

Dual control exerted by dopamine in blood-progenitor cell cycle regulation inDrosophila

Kapoor

Padmavathi

Mukherjee

2021

Preprint

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In Drosophila, definitive hematopoiesis occurs in a specialized organ termed "lymph gland", where multi-potent stem-like blood progenitor cells reside and their homeostasis is central to growth of this organ. Recent findings have implicated a reliance on neurotransmitters in progenitor development and function however, our understanding of these molecules is still limited. Here, we extend our analysis and show that blood-progenitors are self-sufficient in synthesizing dopamine, a well-established neurotransmitter and have modules for its sensing through receptor and uptake via, transporter. Modulating their expression in progenitor cells affects lymph gland growth. Progenitor cell cycle analysis revealed an unexpected requirement for intracellular dopamine in progression of early progenitors from S to G2 phase of the cell cycle, while activation of dopamine-receptor later in development regulated the progression from G2 to entry into mitosis. The dual capacity in which dopamine operates, both intra-cellularly and extra-cellularly, controls lymph gland growth. These data highlight a novel and non-canonical use of dopamine as a proliferative cue by the myeloid-progenitor system and reveals a functional requirement for intracellular dopamine in cell-cycle progression.

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Section: Resultsmentioning

confidence: 81%

Dual control exerted by dopamine in blood-progenitor cell cycle regulation inDrosophila

Kapoor

Padmavathi

Mukherjee

2021

Preprint

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“…Its usefulness is in that it provides a broad landscape for gene expression. However, in the case of the lymph gland, a finer analysis at a cellular level is warranted because of the considerable heterogeneity reported amongst the cells belonging to individual zones (Jung et al 2005; Kurucz et al 2007; Oyallon et al 2016; Baldeosingh et al 2018; Blanco-Obregon et al 2020). We therefore use single cell RNA-Seq to complement and enhance the bulk RNA-Seq data and to characterize subpopulations of cells that reside within each zone.…”

Section: Resultsmentioning

confidence: 99%

Paths and Pathways that Generate Cell-Type Heterogeneity and Developmental Progression in Hematopoiesis

Girard

Goins

Vuu

et al. 2021

Preprint

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Mechanistic studies of Drosophila lymph gland hematopoiesis are limited by the availability of cell-type specific markers. Using a combination of bulk RNA-Seq of FACS-sorted cells, single cell RNA-Seq and genetic dissection, we identify new blood cell subpopulations along a developmental trajectory with multiple paths to mature cell types. This provides functional insights into key developmental processes and signaling pathways. We highlight metabolism as a driver of development, show that graded Pointed expression allows distinct roles in successive developmental steps, and that mature crystal cells specifically express an alternate isoform of Hypoxia-inducible factor (Hif/Sima). Mechanistically, the Musashi-regulated protein Numb facilitates Sima-dependent non-canonical, while inhibiting canonical, Notch signaling. Broadly, we find that prior to making a fate choice, a progenitor selects between alternative, biologically relevant, transitory states allowing smooth transitions reflective of combinatorial expressions rather than stepwise binary decisions. Increasingly, this view is gaining support in mammalian hematopoiesis.

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“…We took advantage of known differences in the expression patterns of two progenitor drivers (Tep4-GAL4 92,93 and dome MESO -GAL4 32,92,94,95 ) to better understand the spatial regulation of the cell cycle. While dome MESO -GAL4 is ubiquitously active in all progenitors, Tep4-GAL4 expression is confined to an inner subset of less mature dome MESO -expressing cells, which have been referred to as "core progenitors", located closer to the dorsal vessel and farther away from the edge of the lymph gland [36][37][38][39] . The distinction in the expression of these two drivers is best appreciated in live imaging of the larva (Figure 5M-O).…”

Section: Spatial Regulation Of the Cell Cyclementioning

confidence: 99%

“…Recent genetic [36][37][38][39] and transcriptomic studies 40,41 have identified considerable heterogeneity within the progenitor population. These subpopulations are spatially arranged so that the innermost ones ("core" progenitors), closest to the dorsal vessel, are the least mature, while the most mature ones ("distal" progenitors) are found at the periphery of the MZ near the site of differentiation.…”

Section: Introductionmentioning

confidence: 99%

Wnt signaling couples G2 phase control with differentiation during hematopoiesis

Goins,

Girard,

Mondal

et al. 2023

Preprint

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During homeostasis, a critical balance is maintained between myeloid-like progenitors and their differentiated progeny, which function to mitigate stress and innate immune challenges. The molecular mechanisms that help achieve this balance are not fully understood. Using genetic dissection in Drosophila, we show that a Wnt6/EGFR-signaling network simultaneously controls progenitor growth, proliferation, and differentiation. Unlike G1-quiescence of stem cells, hematopoietic progenitors are blocked in the G2 phase by a beta-catenin-independent Wnt6 pathway that restricts Cdc25 nuclear entry and promotes cell growth. Canonical beta-catenin-dependent Wnt6 signaling is spatially confined to mature progenitors through localized activation of the tyrosine-kinases EGFR and Abl, which promote nuclear entry of beta-catenin and facilitate exit from G2. This strategy combines transcription-dependent and -independent forms of both Wnt6 and EGFR pathways to create a direct link between cell-cycle control and differentiation. This unique combinatorial strategy employing conserved components may underlie homeostatic balance and stress response in mammalian hematopoiesis.

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Context-specific functions of Notch in Drosophila blood cell progenitors

Abstract: statement Notch signaling regulates differently distinct populations of blood cell progenitors of the Drosophila larval hematopoietic organ.

Cited by 5 publications

References 49 publications

Dual control exerted by dopamine in blood-progenitor cell cycle regulation inDrosophila

Dual control exerted by dopamine in blood-progenitor cell cycle regulation inDrosophila

Paths and Pathways that Generate Cell-Type Heterogeneity and Developmental Progression in Hematopoiesis

Wnt signaling couples G2 phase control with differentiation during hematopoiesis

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