Polyploidy promotes transformation of epithelial cells into nonprofessional phagocytes

• 成果类型: Article
• 署名作者: Huang, Yi-Chun; Costa, Caique Almeida Machado; Ruiz, Nicolas Vergara; Wang, Xianfeng; Jevitt, Allison; Breneman, Christina Marie; Han, Chun; Deng, Wu-Min
• 署名单位: Tulane University; Tulane University Hospital; Cornell University; College of Charleston
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9623
• DOI: 10.1073/pnas.2427293122
• 发表日期: 2025-07-22
• 关键词: drosophila follicle cells; n-terminal kinase; caspase activity; death; notch; engulfment; morphogenesis; draper; differentiation; activation

摘要

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, nonprofessional 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 (FCs) into NPPs is dependent on Notch signaling activation during mid-oogenesis. Moreover, Notch over-activation 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 FCs 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.