Biology subjects

Deng, W.-M.

Publications and source records attributed to Deng, W.-M..

12 recordsLinked to original sources

bioRxiv2026

Live Imaging of Epithelial Phagocyte Differentiation in the Drosophila Ovary RevealsTransient and Novel Behaviors

The transformation of epithelial cells into Non-Professional Phagocytes (NPPs) is a conserved and versatile adaptation that occurs in response to immune challenges, tissue remodeling, and apoptotic debris clearance. In the Drosophila melanogaster ovary, follicle cells (FCs) acquire phagocytic capabilities under stress, providing a powerful model to study this process. Using time-lapse live imaging, we captured dynamic behaviors associated with FC-to-NPP differentiation that are too transient to detect by static imaging. Our approach confirmed established features, including germline cell death, cytoplasmic expansion, and debris engulfment, and revealed previously unrecognized capabilities. These include a gradual increase in JNK pathway activation, after which NPPs exhibit collective migration toward dying germline cells, epithelial delamination, long-range target capture through pseudopodial extensions, and the engulfment of neighboring FCs. These findings demonstrate that epithelial-derived NPPs can perform complex phagocytic tasks typically attributed to professional phagocytes such as macrophages. Our work establishes the Drosophila ovary as a robust in vivo system to uncover conserved and novel aspects of epithelial plasticity and phagocytic function, particularly those involving transient behaviors missed by fixed-sample analyses.

cell biology↗

bioRxiv2026

Leptin Acts as a Peripheral Tropic Signal to Tune Steroidogenesis

The integration of metabolic status with reproductive and developmental timing is a cornerstone of animal physiology, yet how steroidogenesis rapidly adapts to abrupt environmental changes remains poorly understood. Here, we identify a peptide hormone circuit in which leptin or its analogs act as peripheral tropic signals, directly coupling systemic metabolic state to steroid hormone production through dynamic remodeling of intracellular lipid pools. Mechanistically, spatiotemporal fluctuations in leptin activate JAK/STAT signaling within steroidogenic tissues to reprogram the balance among lipid droplets, cholesteryl esters, and free cholesterol, thereby tuning the amplitude and timing of steroid hormone pulses via hormone-sensitive lipase (Hsl), a rate-limiting determinant of steroidogenic flux. Cross-species analyses in Drosophila melanogaster, Blattella germanica, and Mus musculus suggest a partially conserved leptin-JAK/STAT-lipase axis that functions as a metabolic "sterol rheostat", enabling rapid modulation of steroidogenesis in response to systemic metabolic and stress cues. These findings reveal a metabolic-endocrine mechanism by which leptin can act directly on steroidogenic organs to regulate hormonal output.

developmental biology↗

bioRxiv2026

Tumor-induced species-specific dysbiosis drives renal innate immunity and nephrogenic ascites

Ascites is a life-threatening complication of advanced malignancies, yet how tumors disrupt systemic fluid homeostasis remains poorly understood. Here, using a Drosophila tumor allograft model that recapitulates key features of cancer-associated ascites, we identify a tumor-microbiome-renal axis that controls host fluid balance. Tumor-bearing hosts develop severe abdominal fluid accumulation accompanied by marked expansion and systemic dissemination of the gut commensal Acetobacter aceti. Tumor-induced bacterial dissemination activates innate immune signaling in the Malpighian tubules, the insect renal tubules, leading to uric acid accumulation, nephrolithiasis, and progressive ascites. Selective elimination of A. aceti, or renal-tubule-specific suppression of IMD/NF-{kappa}B signaling, abolishes these pathological changes. Conversely, mono-association of axenic hosts with A. aceti is sufficient to recapitulate the ascites phenotype through IMD pathway activation. Together, these findings demonstrate that tumors can remotely induce nephrogenic pathology through species-specific microbiome-dependent immune activation, establishing a mechanistic link between cancer progression and systemic fluid imbalance.

cancer biology↗

bioRxiv2025

Polyploidy promotes transformation of epithelial cells into non-professional phagocytes

Removal of dead and damaged cells is critical for organismal health. Under stress conditions such as nutritional deprivation, infection, or temperature shift, the clearance of nonessential cells becomes a universal strategy to conserve energy and maintain tissue homeostasis. Typically, this task is performed by professional phagocytes such as macrophages. However, non-professional phagocytes (NPPs) can also adopt a phagocytic fate under specific circumstances. Similar to professional phagocytes, NPPs undergo transitions from immature to mature states and activation, but the precise cellular and molecular mechanisms governing their maturation, induction and phagocytic execution remain largely unknown. A notable example of stress-induced phagocytosis is the removal of germline cells by follicle cell-derived NPPs during oogenesis in Drosophila. In this study, we report that the transformation of follicle cells into NPPs is dependent on Notch signaling activation during mid-oogenesis. Moreover, Notch overactivation is sufficient to trigger germline cell death and clearance (GDAC). We further show that polyploidy, driven by Notch signaling-induced endoreplication, is essential for the transformation of follicle cells into NPPs. Polyploidy facilitates the activation of JNK signaling, which is crucial for the phagocytic behavior of these cells. Additionally, we show that polyploidy in epidermal cells, another type of NPPs, is important for their engulfment of dendrites during induced degeneration. Together, these findings suggest that polyploidy is a critical factor in the transformation of epithelial cells into NPPs, enabling their phagocytic functions, which are essential for maintaining cellular and organismal homeostasis during stress conditions. SIGNIFICANCEThe ability to remove dead and damaged cells is essential for maintaining tissue homeostasis and organismal health. While this task is typically performed by professional phagocytes such as macrophages, non-professional phagocytes (NPPs) can also acquire phagocytic functions during development or in response to stress conditions. Using Drosophila oogenesis as a model, we reveal that the transformation of follicle cells into NPPs is driven by Notch signaling and is critically dependent on polyploidy. Our findings show that polyploidy, induced through Notch signaling-mediated endoreplication, is required for activating JNK signaling, a pathway essential for the phagocytic behavior of NPPs. Furthermore, we show that polyploidy also facilitates the phagocytic activity of epidermal cells in clearing degenerating dendrites. Together, these results suggest that polyploidy plays an important role in enabling epithelial cells to adopt NPP functions and in maintaining tissue and organismal homeostasis under stress conditions.

developmental biology↗

bioRxiv2024

Topoisomerase I is an Evolutionarily Conserved Key Regulator for Satellite DNA Transcription

Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of -satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, -satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced -satellite RNAs were predominantly derived from the -satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

cell biology↗

bioRxiv2023

Integrating lipid metabolism, pheromone production and perception by Fruitless and Hepatocyte nuclear factor 4

Sexual attraction and perception, governed by separate genetic circuits in different organs, are crucial for mating and reproductive success, yet the mechanisms of how these two aspects are integrated remain unclear. In Drosophila, the male-specific isoform of Fruitless (Fru), FruM, is known as a master neuro-regulator of innate courtship behavior to control perception of sex pheromones in sensory neurons. Here we show that the non-sex specific Fru isoform (FruCOM) is necessary for pheromone biosynthesis in hepatocyte-like oenocytes for sexual attraction. Loss of FruCOM in oenocytes resulted in adults with reduced levels of the cuticular hydrocarbons (CHCs), including sex pheromones, and show altered sexual attraction and reduced cuticular hydrophobicity. We further identify Hepatocyte nuclear factor 4 (Hnf4) as a key target of FruCOM in directing fatty acid conversion to hydrocarbons in adult oenocytes. fru- and Hnf4-depletion disrupts lipid homeostasis, resulting in a novel sex-dimorphic CHC profile, which differs from doublesex- and transformer-dependent sexual dimorphism of the CHC profile. Thus, Fru couples pheromone perception and production in separate organs for precise coordination of chemosensory communication that ensures efficient mating behavior. TeaserFruitless and lipid metabolism regulator HNF4 integrate pheromone biosynthesis and perception to ensure robust courtship behavior.

developmental biology↗

bioRxiv2022

Cell polarity opposes Jak-STAT mediated Escargot activation that drives intratumor heterogeneity in a Drosophila tumor model

In proliferating neoplasms, microenvironment-derived selective pressures promote tumor heterogeneity by imparting diverse capacities for growth, differentiation and invasion. However, what makes a tumor cell respond to signaling cues differently from a normal cell is not well understood. In the Drosophila ovarian follicle cells, apicobasal-polarity loss induces heterogenous epithelial multilayering. When exacerbated by oncogenic-Notch expression, this multilayer displays an increased consistency in the occurrence of morphologically distinguishable cells adjacent to the polar follicle cells. Polar cells release the Jak-STAT ligand Unpaired (Upd), in response to which, neighboring polarity-deficient cells exhibit a precursor-like transcriptomic state. Using single-cell transcriptomics, we discovered the ectopic activation of the Snail-family transcription factor Escargot (Esg) in these cells. We also characterized similar relationship between Upd and Esg during early follicular development, where the establishment of polarity determines follicle-cell differentiation. Overall, our results indicate that epithelial-cell polarity acts as a gatekeeper against microenvironmental selective pressures that drive heterogeneity.

cancer biology↗

bioRxiv2022

Single-cell transcriptomics identifies regulation of invasive behavior in Drosophila follicle cells with polarity loss

Apicobasal cell-polarity loss is a founding event in Epithelial-Mesenchymal Transition (EMT) and epithelial tumorigenesis, yet how pathological polarity loss induces plasticity changes remains largely unknown. To understand the mechanisms and mediators regulating plasticity upon polarity loss, we performed single-cell (sc) RNA sequencing of Drosophila ovaries, where inducing polarity-gene l(2)gl knockdown (Lgl-KD) causes invasive delamination of the follicular epithelia. Integrating Lgl-KD with the corresponding wild-type sc-transcriptome, we discovered clusters specific to various discernible phenotype-specific cell types and further characterized the regulons active in those cells. A genetic requirement of Keap1-Nrf2 signaling in promoting multilayer formation of Lgl-KD cells was further identified. Elevated expression of Keap1 increased the volume of delaminated follicle cells that undergo enhanced collective invasion via cytoskeletal remodeling. Overall, our findings describe the comprehensive transcriptome of the follicle-cell tumor model at the single-cell resolution and identify a previously unappreciated link between stress signaling and cell plasticity in early tumorigenesis.

developmental biology↗

bioRxiv2021

Re-entry into mitosis and regeneration of intestinal stem cells through enteroblast dedifferentiation in Drosophila midguts

Many adult tissues and organs including the intestine rely on resident stem cells to maintain homeostasis. In mammalian intestines, upon ablation of resident stem cells, the progenies of intestinal stem cells (ISCs) such as secretory cells and tuft cells can dedifferentiate to generate ISCs to drive epithelial regeneration, but whether and how the ISC progenies dedifferentiate to generate ISCs under physiological conditions remains unknown. Here we show that infection of pathogenic bacteria induces enteroblasts (EBs) as one type of ISC progenies to re-enter the mitotic cycle in the Drosophila intestine. The re-entry into mitosis is dependent on epithermal growth factor receptor (EGFR)-Ras signaling and ectopic activation of EGFR-Ras signaling in EBs is sufficient to drive EBs cell-autonomously to re-enter into mitosis. In addition, we examined whether EBs gain ISC identity as a prerequisite to divide, but the immunostaining with stem cell marker Delta shows that these dividing EBs do not gain ISC identity. After employing lineage tracing experiments, we further demonstrate that EBs dedifferentiate to generate functional ISCs after symmetric divisions of EBs. Together, our study in Drosophila intestines uncovers a new role of EGFR-Ras signaling in regulating re-entry into mitosis and dedifferentiation during regeneration and reveals a novel mechanism by which ISC progenies undergo dedifferentiation through a mitotic division, which has important implication to mammalian tissue homeostasis and tumorigenesis.

cell biology↗

bioRxiv2020

Developmental regulation of oocyte lipid uptake via 'patent' tricellular junctions in Drosophila epithelium

Epithelia form protective permeability barriers that selectively allow the exchange of material while maintaining tissue integrity under extreme mechanical, chemical, and bacterial loads. Here, we report in the Drosophila follicular epithelium a developmentally regulated and evolutionarily conserved process, patency, wherein a breach is created in the epithelium at tricellular contacts during mid-vitellogenesis. In Drosophila, patency exhibits a strict temporal range delimited by the transcription factor Tramtrack69, and a spatial pattern regulated by the dorsal-anterior signals of the follicular epithelium. Crucial for lipid uptake by the oocyte, patency is also exploited by endosymbionts such as Spiroplasma pulsonii. Our findings reveal an evolutionarily conserved non-typical epithelial function in a classic model system.

developmental biology↗

bioRxiv2019

Single-cell RNA sequencing of adult Drosophila ovaryidentifies transcriptional programs governing oogenesis

Oogenesis is a complex developmental process that involves spatiotemporally regulated coordination between the germline and supporting, somatic cell populations. This process has been modelled extensively using the Drosophila ovary. While different ovarian cell types have been identified through traditional means, the large-scale expression profiles underlying each cell type remain unknown. Using single-cell RNA sequencing technology, we have built a transcriptomic dataset for the adult Drosophila ovary and connected tissues. This dataset captures the entire transcriptional trajectory of the developing follicle cell population over time. Our findings provide detailed insight into processes such as cell-cycle switching, migration, symmetry breaking, nurse cell engulfment, egg-shell formation, and signaling during corpus luteum formation, marking a newly identified oogenesis-to-ovulation transition. Altogether, these findings provide a broad perspective on oogenesis at a single-cell resolution while revealing new genetic markers and fate-specific transcriptional signatures to facilitate future studies.

developmental biology↗

bioRxiv2018

Germline silencing of UASt depends on the piRNA pathway

One of the most extensively used techniques in Drosophila is the Gal4/UAS binary system, which allows tissue-specific misexpression or knockdown of specific genes of interest. The original UAS vector, UASt, can only be activated for transgene expression in somatic tissues and not in the germline cells. Rorth (1998) generated UASp, a modified UAS vector that is responsive to Gal4 in both somatic and germline tissues, by replacing both the hsp70 promoter and the SV40 3UTR with the P transposase promoter and the K10 3UTR respectively. At present, the mechanisms by which UASt is silenced in germline cells are not fully understood. Here, we report that the piRNA pathway is involved in suppressing UASt expression in ovarian germline cells. Individually knocking down or mutating components of the piRNA biogenesis pathway (e.g., Piwi, AGO3, Aub, Spn-E, and Vasa) resulted in the expression of the UASt-reporter (GFP or RFP) in the germline. An RNA-seq analysis of small RNAs revealed that the hsp70 promoter of UASt is targeted by piRNAs, and in the aub mutant ovary, the amount of piRNAs targeting the hsp70 promoter is reduced by around 40 folds. In contrast, the SV40 3UTR of the UASt, which happens to be targeted by the Nonsense-mediated RNA decay (NMD) pathway, is not responsible for germline UASt suppression, as UASt-reporters with NMD-insensitive 3UTRs fail to show germline expression. Taken together, our studies reveal a crucial role of the piRNA pathway, potentially via the suppression of the hsp70 promoter, in germline UASt silencing in Drosophila ovaries.

genetics↗