A scalable human-zebrafish xenotransplantation model reveals gastrosome-mediated processing of dying neurons by human microglia

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https://rdp.sfb274.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/408885537 (DFG Gepris entry) The central nervous system (CNS) is a terminally differentiated tissue, where any insult carries a heightened risk - yet the tissue response to these insults is variable and can range from irreversible destruction to almost complete recovery. The rules that instruct these divergent outcomes are still unknown. The aim of this CRC is therefore to understand the biology of the multicellular ...

Despite the critical role of microglia in human brain pathologies, the molecular mechanisms that govern the diverse and context-dependent set of phenotypes are poorly understood. This project will introduce a highly versatile human brain organoid-based in vivo platform for investigating human glial cells that operate within a vascularized human brain-like environment. Using this platform, we aim to dissect the molecular networks that control human microglia cell responses during CNS injury in ...

Microglia engulf dying neurons through efferocytosis, a critical function in both development and disease. How microglia process the engulfed neuronal material—especially lipids—remains poorly understood, despite its central role in neurodegeneration. Thus, we developed HuZIBRA, a scalable in vivo xenotransplantation model in which human iPSC-derived microglia-like cells (iMGLs) are introduced into the developing zebrafish brain (zf-hiMG), a system characterized by high levels of neuronal cell ...