Cadherin-11 regulates mesenchymal stem cell differentiation into smooth muscle cells and development of contractile function in vivo

Alimperti, Stella; You, Hui; George, Teresa; Agarwal, Sandeep K.; Andreadis, Stelios T.

doi:10.1242/jcs.134833

Cited by 75 publications

(40 citation statements)

References 92 publications

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“…Recently, our group reported that CDH11 but not CDH2 was necessary for MSC differentiation into SMCs [9] (Fig. 3).…”

Section: The Role Of Cdh2 and Cdh11 In Mesenchymal Stem Cell Diffementioning

confidence: 99%

“…However, the mechanical and biochemical signals originating from cell-cell adhesion remain relatively unexplored in this context. Recent studies implicated adherens junctions in the maintenance of embryonic stem cell self-renewal potential, cellular reprogramming, hematopoietic stem cell engraftment and mesenchymal stem cell (MSC) differentiation into muscle [8, 9, 18]. Here we provide a brief review on the role of cadherins, in particular CDH2 and CDH11, in development and stem cell fate decisions.…”

Section: Introductionmentioning

confidence: 99%

“…For example, it is well established that the process of Epithelial to Mesenchymal Transition (EMT) is characterized by augmented expression of CDH2 and CDH11 and diminished expression of CDH1 [5–7]. Recent studies suggest that cadherin expression and cell-cell adhesion may also be critical in other transitions between cellular states such as lineage specification of stem cells or reprogramming of adult cells to a pluripotent state [8, 9]. …”

Section: Introductionmentioning

confidence: 99%

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CDH2 and CDH11 act as regulators of stem cell fate decisions

2015

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Accumulating evidence suggests that the mechanical and biochemical signals originating from cell-cell adhesion are critical for stem cell lineage specification. In this review, we focus on the role of cadherin mediated signaling in development and stem cell differentiation, with emphasis on two well-known cadherins, cadherin-2 (CDH2) (N-cadherin) and cadherin-11 (CDH11) (OB-cadherin). We summarize the existing knowledge regarding the role of CDH2 and CDH11 during development and differentiation in vivo and in vitro. We also discuss engineering strategies to control stem cell fate decisions by fine-tuning the extent of cell-cell adhesion through surface chemistry and microtopology. These studies may be greatly facilitated by novel strategies that enable monitoring of stem cell specification in real time. We expect that better understanding of how intercellular adhesion signaling affects lineage specification may impact biomaterial and scaffold design to control stem cell fate decisions in three-dimensional context with potential implications for tissue engineering and regenerative medicine.

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“…Recently, our group reported that CDH11 but not CDH2 was necessary for MSC differentiation into SMCs [9] (Fig. 3).…”

Section: The Role Of Cdh2 and Cdh11 In Mesenchymal Stem Cell Diffementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CDH2 and CDH11 act as regulators of stem cell fate decisions

2015

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“…19,20 Fibroblasts play a critical role in wound closure through its contractile function as well as synthesis and remodeling of extracellular matrix (ECM), mainly collagen. Interestingly, loss of CDH11 diminished several key biological functions in smooth muscle, hair follicle, and fibroblast cells, including contractility, 21 migration capacity, 12 and ECM synthesis, 22 ultimately compromising the tissue mechanical properties. CDH11 was also reported to play a role in the response of fibroblasts to inflammatory mediators such as TNF-α.…”

Section: Introductionmentioning

confidence: 99%

Cadherin‐11 binds to PDGFRβ and enhances cell proliferation and tissue regeneration via the PDGFR‐AKT signaling axis

et al. 2020

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Intercellular adhesion through homotypic interaction between cadherins regulates multiple cellular processes including cytoskeletal organization, proliferation, and survival. In this paper, we provide evidence that cadherin‐11 (CDH11) binds to and promotes cell proliferation both in vitro and in vivo in synergy with the platelet‐derived growth factor receptor beta (PDGFRβ). Engagement of CDH11 increased the sensitivity of cells to PDGF‐BB by 10‐ to 100‐fold, resulting in rapid and sustained phosphorylation of AKT, ultimately promoting and cell proliferation and tissue regeneration. Indeed, wound healing experiments showed that healing was severely compromised in Cdh11−/− mice, as evidenced by significantly decreased proliferation, AKT phosphorylation, and extracellular matrix (ECM) synthesis of dermal cells. Our results shed light into understanding how intercellular adhesion can promote cell proliferation and may have implications for tissue regeneration and cancer progression.

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“…12 Although there is limited information on atypical cadherins in vascular cells, cadherin-11 has been reported to be upregulated in SMCs in vein grafts 28 and required for in vitro differentiation of mesenchymal stem cells to SMCs. 29 The current findings are the first to establish a role for cadherin-11 in structural networking among SMCs. Recent adhesion force measurements by Hinz et al 30 have established that cadherin-11 bonds are stronger than those of N-cadherin.…”

Section: Arterioscler Thromb Vasc Biol May 2015mentioning

confidence: 54%

Collectivization of Vascular Smooth Muscle Cells via TGF-β–Cadherin-11–Dependent Adhesive Switching

Balint

Yin

Chakrabarti

et al. 2015

ATVB

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Objective-Smooth muscle cells (SMCs) in healthy arteries are arranged as a collective. However, in diseased arteries, SMCs commonly exist as individual cells, unconnected to each other. The purpose of this study was to elucidate the events that enable individualized SMCs to enter into a stable and interacting cell collective. Approach and Results-Human SMCs stimulated to undergo programmed collectivization were tracked by time-lapse microscopy. We uncovered a switch in the behavior of contacting SMCs from semiautonomous motility to cell-cell adherence. Central to the cell-adherent phenotype was the formation of uniquely elongated adherens junctions, up to 60 μm in length, which appeared to strap adjacent SMCs to each other. Remarkably, these junctions contained both N-cadherin and cadherin-11. Ground-state depletion super-resolution microscopy revealed that these hybrid assemblies were comprised of 2 parallel nanotracks of each cadherin, separated by 50 nm. Blocking either N-cadherin or cadherin-11 inhibited collectivization. Cell-cell adhesion and adherens junction elongation were associated with reduced transforming growth factor-β signaling, and exogenous transforming growth factor-β1 suppressed junction elongation via the noncanonical p38 pathway. Imaging of fura-2-loaded SMCs revealed that SMC assemblies displayed coordinated calcium oscillations and cell-cell transmission of calcium waves which, together with increased connexin 43-containing junctions, depended on cadherin-11 and N-cadherin function. Conclusions-SMCs can self-organize, structurally and functionally, via transforming growth factor-β-p38-dependent adhesive switching and a novel adherens junction architecture comprised of hybrid nanotracks of cadherin-11 and N-cadherin. The findings define a mechanism for the assembly of SMCs into networks, a process that may be relevant to the stability and function of blood vessels.

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Cadherin-11 regulates mesenchymal stem cell differentiation into smooth muscle cells and development of contractile function in vivo

Cited by 75 publications

References 92 publications

CDH2 and CDH11 act as regulators of stem cell fate decisions

CDH2 and CDH11 act as regulators of stem cell fate decisions

Cadherin‐11 binds to PDGFRβ and enhances cell proliferation and tissue regeneration via the PDGFR‐AKT signaling axis

Collectivization of Vascular Smooth Muscle Cells via TGF-β–Cadherin-11–Dependent Adhesive Switching

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