Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells

Abstract

The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation.

Actomyosin contractility plays a role in MAP2 expression during nanotopography-directed neuronal differentiation of human embryonic stem cells

“…Several studies have previously shown that Wnt is the main player during osteogenic differentiation of mesenchymal stem cells on microstructured titanium surfaces [33e35]. Studies have also demonstrated that Wnt canonical signaling was mediated by the change in cytoskeletal structure, more specifically the primary cilia length, when grown on topographies [36,37]. Taken together, we speculate that the grooved topography caused cytoskeletal rearrangement of hESC and thereby resulted in the upregulation of WNT1.…”

Organizational metrics of interchromatin speckle factor domains: integrative classifier for stem cell adhesion & lineage signaling

“…Microenvironmental cues, specifically soluble factors, topography, and substrate surface functionality, have been shown modulate hMSC differentiation through β-catenin 42, 51 , FAK 52, 53 , and RhoGTPase 54 , which are key signaling molecules that direct osteogenic differentiation 18, 55, 56 . Surface topography modulates Wnt/β-catenin signaling through primary cilia structure 42 , and increased Wnt/β-catenin is observed in hMSCs cultured on rough topographies 57 .…”

Unbiased Analysis of the Impact of Micropatterned Biomaterials on Macrophage Behavior Provides Insights beyond Predefined Polarization States

“…Substrate topography affects factors such as cell attachment, cytoskeleton organisation, and cell and nuclear shape and orientation [27][28][29][30] Thus, in this study we first used soft photolithography to fabricate micropattenred GelMA hydrogels followed by investigating the response of human monocyte-derived macrophages to such different microtopographies. We mainly focused on two topographies namely micropillars (height=20 μm, diameter=20 μm, distance between pillars=5 μm) and microgrooves/ridges (depth=20 μm, groove width=20 μm, ridge width=10 μm) to determine the effect of focal point adhesion (micropillars) and cell elongation (microgrooves/ridges) on macrophage phenotype and function using conventional markers (i.e.…”