SEMINAR:From Gut to Liver: Assembloid Platforms Revealing Conserved Principles of Tissue Remodeling

Guest: Bahar Degirmenci Uzun, Bilkent University

Title: From Gut to Liver: Assembloid Platforms Revealing Conserved Principles of Tissue Remodeling (BIO)

Date/Time: December 24, 2025, 13:40

Location: FENS G035

Abstract: How adult organs sense injury and decide whether to regenerate, remodel, or scar is encoded in multicellular niches that integrate mechanical, metabolic, and inflammatory cues. In this talk, I will present two first-in-field assembloid platforms that uncover conserved principles of such niche-driven plasticity in the intestine and liver. First, we develop murine ENS-rich assembloids that self-organize to recapitulate the cellular diversity, epithelial architecture, and functional circuitry of native colonic tissue, enabling controlled interrogation of enteric nervous system (ENS) dynamics. By integrating this platform with an in vivo colitis model, we show that inflammation triggers coordinated reorganization of S100b⁺ glial cells, TUJ1⁺ neurons, PDGFRA⁺ mesenchymal cells, and epithelial cells, revealing pleiotrophin-PTPRZ1 signaling as a key pathway promoting neural elongation and strengthening neuron-glia interactions. We further demonstrate that activated neurons transfer lipids to glia during inflammation, positioning enteric glia as metabolic and structural hubs that safeguard neuronal integrity and foster tissue regeneration. In parallel, we introduce a multicellular liver assembloid that combines bi-potent ductal organoids differentiated into hepatocyte-like organoids with cholangiocytes to reconstruct a periportal-like niche with a continuous bile canaliculi-duct interface. This model preserves spatial organization, bile transport, and secretory function, and allows us to implicate a cholangiocyte mechanotransduction pathway in which the ion channel PIEZO1 regulates YAP1 activity to steer progenitor lineage profiles and coordinate cholangiocyte-driven remodeling under fibrotic stress. Together, these assembloid systems provide a mechanistic framework for how tissue-resident support cells - enteric glia and cholangiocytes - sense and transduce environmental signals to orchestrate organ plasticity, regeneration, and disease-associated remodeling.

Bio: Her research focuses on stem cell biology and organoid/assembloid models to understand how multicellular niches regulate tissue homeostasis, regeneration, and remodeling. She received her B.Sc. in Biological Sciences from Middle East Technical University (METU) and her M.Sc. from Koç University, where she worked on rational drug design targeting Aurora B kinase. She then completed her Ph.D. at the University of Zurich, studying how Wnt-secreting stem cell niches control intestinal renewal, regeneration and cancer. She is currently an Assistant Professor in the Department of Molecular Biology and Genetics at Bilkent University in Ankara, Turkey.