Patterning of human epidermal stem cells on undulating elastomer substrates reflects differences in cell stiffness

Mobasseri, S A; Zijl, Sebastiaan; Salameti, Vasiliki; Walko, Gernot; Stannard, Andrew; Garcia-Manyes, Sergi; Watt, Fiona M.

doi:10.1016/j.actbio.2019.01.063

Cited by 45 publications

(45 citation statements)

References 32 publications

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“…Given accumulating evidence of nuclear mechano-transduction processes 27,39-41 we then investigated how these physical changes translated into mechano-responses and biochemical changes within the cells as a function of local curvature. We showed that the patterns of cellular densities generated by the matrix curvature are associated with significant changes in the spatial distribution of YAP 2,3 , consistent with the idea of curvature-sensing occurring via physically-driven thickness/density-changes. YAP in particular has been shown to be is a key transcription factor that mediates the interplay between cellular mechanics and signaling cascades underlying gene expression, cell proliferation, differentiation fate decisions, and organ development.…”

Section: Discussionsupporting

confidence: 79%

Large-scale curvature sensing by epithelial monolayers depends on active cell mechanics and nuclear mechanoadaptation

Luciano

Xue

Vos

et al. 2020

Preprint

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AbstractWhile many tissues fold in vivo in a highly reproducible and robust way, epithelial folds remain difficult to reproduce in vitro, so that the effects and underlying mechanisms of local curvature on the epithelial tissue remains unclear. Here, we photoreticulated polyacrylamide hydrogels though an optical photomask to create corrugated hydrogels with isotropic wavy patterns, allowed us to show that concave and convex curvatures affect cellular and nuclear shape. By culturing MDCK epithelial cells at confluency on corrugated hydrogels, we showed that the substrate curvature leads to thicker epithelial zones in the valleys and thinner ones on the crest, as well as corresponding density, which can be generically explained by a simple 2D vertex model, leading us to hypothesize that curvature sensing could arise from resulting density/thickness changes. Additionally, positive and negative local curvatures lead to significant modulations of the nuclear morphology and positioning, which can also be well-explained by an extension of vertex models taking into account membrane-nucleus interactions, where thickness/density modulation generically translate into the corresponding changes in nuclear aspect ratio and position, as seen in the data. Consequently, we find that the spatial distribution of Yes associated proteins (YAP), the main transcriptional effector of the Hippo signaling pathway, is modulated in folded epithelial tissues according to the resulting thickness modulation, an effect that disappears at high cell density. Finally, we showed that these deformations are also associated with changes of A-type and B-type lamin expression, significant chromatin condensation and to lower cell proliferation rate. These findings show that active cell mechanics and nuclear mechanoadaptation are key players of the mechanistic regulation of epithelial monolayers to substrate curvature, with potential application for a number of in vivo situations.

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Section: Discussionsupporting

confidence: 79%

Large-scale curvature sensing by epithelial monolayers depends on active cell mechanics and nuclear mechanoadaptation

Luciano

Xue

Vos

et al. 2020

Preprint

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“…Therefore, their action could be affected by direct interactions with key lipids within membranes or by changes in their local environment due to lipid variation. Lipid composition can affect the stiffness and mechanosensitivity of plasma membranes ( 44 – 46 ), and differences in the stiffness of epidermal stem cells and neighboring basal cells in culture were recently reported ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Human epidermal stem cell differentiation is modulated by specific lipid subspecies

Rudan

Mishra

Klose

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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While the lipids of the outer layers of mammalian epidermis and their contribution to barrier formation have been extensively described, the role of individual lipid species in the onset of keratinocyte differentiation remains unknown. A lipidomic analysis of primary human keratinocytes revealed accumulation of numerous lipid species during suspension-induced differentiation. A small interfering RNA screen of 258 lipid-modifying enzymes identified two genes that on knockdown induced epidermal differentiation: ELOVL1, encoding elongation of very long-chain fatty acids protein 1, and SLC27A1, encoding fatty acid transport protein 1. By intersecting lipidomic datasets from suspension-induced differentiation and knockdown keratinocytes, we pinpointed candidate bioactive lipid subspecies as differentiation regulators. Several of these—ceramides and glucosylceramides—induced differentiation when added to primary keratinocytes in culture. Our results reveal the potential of lipid subspecies to regulate exit from the epidermal stem cell compartment.

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“…Human BM exhibits undulations and epidermal stem cell patterning is dependent on mechanical forces exerted at intercellular junctions. Cell density is highest, and thus cell-matrix adhesion area the lowest, at the bases of undulations, whereas stem cells accumulate at tips (Helling et al 2019;Mobasseri et al 2019).…”

Section: Matrix Rigidity and Topologymentioning

confidence: 99%

Mechanical Forces in the Skin: Roles in Tissue Architecture, Stability, and Function

Biggs

Kim

Miroshnikova

et al. 2020

Journal of Investigative Dermatology

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Tissue shape emerges from the collective mechanical properties and behavior of individual cells and the ways by which they integrate into the surrounding tissue. Tissue architecture and its dynamic changes subsequently feed back to guide cell behavior. The skin is a dynamic, self-renewing barrier that is subjected to large-scale extrinsic mechanical forces throughout its lifetime. The ability to withstand this constant mechanical stress without compromising its integrity as a barrier requires compartment-specific structural specialization, and capability to sense and adapt to mechanical cues. This review discusses the unique mechanical properties of the skin and the importance of signals that arise from mechanical communication between cells and their environment. Adams JC, Watt FM. Fibronectin inhibits the terminal differentiation of human keratinocytes. Nature. 1989;340(6231):307-9 Adams JC, Watt FM. Changes in keratinocyte adhesion during terminal differentiation: Reduction in fibronectin binding precedes α5β1 integrin loss from the cell surface. Cell. 1990;63(2):425-35 Aw WY, Devenport D. Planar cell polarity: global inputs establishing cellular asymmetry.

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Patterning of human epidermal stem cells on undulating elastomer substrates reflects differences in cell stiffness

Abstract: Graphical abstract

Cited by 45 publications

References 32 publications

Large-scale curvature sensing by epithelial monolayers depends on active cell mechanics and nuclear mechanoadaptation

Large-scale curvature sensing by epithelial monolayers depends on active cell mechanics and nuclear mechanoadaptation

Human epidermal stem cell differentiation is modulated by specific lipid subspecies

Mechanical Forces in the Skin: Roles in Tissue Architecture, Stability, and Function

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