Primary Cilia Are Dysfunctional in Obese Adipose-Derived Mesenchymal Stem Cells

Publication date: Available online 27 January 2018 Source:Stem Cell Reports Author(s): Andreas Ritter, Alexandra Friemel, Nina-Naomi Kreis, Samira Catharina Hoock, Susanne Roth, Ulrikke Kielland-Kaisen, Dörthe Brüggmann, Christine Solbach, Frank Louwen, Juping Yuan Adipose-derived mesenchymal stem cells (ASCs) have crucial functions, but their roles in obesity are not well defined. We show here that ASCs from obese individuals have defective primary cilia, which are shortened and unable to properly respond to stimuli. Impaired cilia compromise ASC functionalities. Exposure to obesity-related hypoxia and cytokines shortens cilia of lean ASCs. Like obese ASCs, lean ASCs treated with interleukin-6 are deficient in the Hedgehog pathway, and their differentiation capability is associated with increased ciliary disassembly genes like AURKA. Interestingly, inhibition of Aurora A or its downstream target the histone deacetylase 6 rescues the cilium length and function of obese ASCs. This work highlights a mechanism whereby defective cilia render ASCs dysfunctional, resulting in diseased adipose tissue. Impaired cilia in ASCs may be a key event in the pathogenesis of obesity, and its correction might provide an alternative strategy for combating obesity and its associated diseases. Graphical abstract Teaser Yuan and colleagues show that primary cilia are deficient in obese adipose-derived mesenchymal stem cells (ASCs). Impaired cilia render ASCs dysfunctional, accounting...

Source: Stem Cell Reports - January 27, 2018 Category: Stem Cells Source Type: research