Project Details
Projekt
Primary cilia dynamics in adipose tissue development and homeostasis
Subject Area
Cell Biology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 503306912
Primary cilia are important regulators of adipose tissue development and function. White adipose tissue (WAT), which stores energy as lipids and is vital for maintaining whole-body energy and immune homeostasis, relies on primary cilia function. This is underlined by a subset of ciliopathies, disorders that arise from cilia dysfunction, which display obesity as a cardinal feature. The differentiation into adipocytes, termed adipogenesis, is highly orchestrated: precursor cells first commit to the adipocyte lineage and then terminally differentiate into adipocytes. Primary cilia are present on pre-adipocytes but are disassembled during proliferation and differentiation. Strikingly, loss of primary cilia formation in pre-adipocytes abolishes differentiation, underlining the importance of primary cilia function for WAT development. However, the stimuli controlling primary cilia signaling and, thereby, pre-adipocyte proliferation and differentiation are largely unknown. Macrophages, one of the major immune cell types in WAT, can influence adipogenesis and contribute to obesity-associated comorbidities. WAT-resident macrophages produce the growth factor PDGFcc, which is required for adipogenesis during development and upon diet-induced obesity. Intriguingly, PDGFs, including PDGFcc, exert their actions via the primary cilium. However, whether macrophage-derived PDGFcc in WAT acts via primary cilia on pre-adipocytes is not known. In this project, we use 2D and 3D cell culture systems in combination with transgenic mouse models to address how signals derived from macrophages affect ciliary protein dynamics and signaling in adipocyte precursors and how this shapes cell fate and function and, thereby, WAT development and homeostasis.
DFG Programme
Research Units
