Matrix remodeling controls a nuclear lamin A/C-emerin network that directs Wnt-regulated stem cell fate

Zhu, Lingxin; Cho, Jung-Sun; Li, Xiaoyan; Weiss, Stephen J.

doi:10.1016/j.devcel.2022.01.015

Cited by 4 publications

(3 citation statements)

References 59 publications

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“…Nuclear lamina-associated lamin A/C determines the localization of emerin, which is an inner nuclear membrane protein [ 48 ]. When lamin A/C is depleted, emerin is no longer localized in the nuclear membrane and instead diffuses within the endoplasmic reticulum (ER) membrane [ 49 ]. In this regard, emerin was mainly confined to the nuclear envelope in macrophages cultured on pTi but was released into the cytoplasm in macrophages cultured on TNTs despite an unchanged protein level (Fig.…”

Section: Resultsmentioning

confidence: 99%

Nanotube patterning reduces macrophage inflammatory response via nuclear mechanotransduction

Zheng

Chen

et al. 2023

J Nanobiotechnol

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The inflammatory immune environment surrounding titanium bone implants determines the formation of osseointegration, and nanopatterning on implant surfaces modulates the immune microenvironment in the implant region. Among many related mechanisms, the mechanism by which nanopatterning controls macrophage inflammatory response still needs to be elucidated. In this paper, we found that inhibition of the nuclear envelope protein lamin A/C by titania nanotubes (TNTs) reduced the macrophage inflammatory response. Knockdown of lamin A/C reduced macrophage inflammatory marker expression, while overexpression of lamin A/C significantly elevated inflammatory marker expression. We further found that suppression of lamin A/C by TNTs limited actin polymerization, thereby reducing the nuclear translocation of the actin-dependent transcriptional cofactor MRTF-A, which subsequently reduced the inflammatory response. In addition, emerin, which is a key link between lamin A/C and actin, was delocalized from the nucleus in response to mechanical stimulation by TNTs, resulting in reduced actin organization. Under inflammatory conditions, TNTs exerted favourable osteoimmunomodulatory effects on the osteogenic differentiation of mouse bone marrow-derived stem cells (mBMSCs) in vitro and osseointegration in vivo. This study shows and confirms for the first time that lamin A/C-mediated nuclear mechanotransduction controls macrophage inflammatory response, and this study provides a theoretical basis for the future design of immunomodulatory nanomorphologies on the surface of metallic bone implants.

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Section: Resultsmentioning

confidence: 99%

Nanotube patterning reduces macrophage inflammatory response via nuclear mechanotransduction

Zheng

Chen

et al. 2023

J Nanobiotechnol

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“…We hypothesized that although TSA restored the expression level of β-catenin and DNA accessibility, β-catenin might still be restricted in the cytoplasm, thereby inhibiting the activation of the Wnt pathway and osteogenic differentiation of the cells. To test this hypothesis, we used Wnt-3a to increase the expression of β-catenin [ 21 ]. Immunofluorescence and western blot analyses revealed a higher nucleus/cytoplasm ratio of β-catenin in the stiff matrix in the presence of Wnt-3a ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Lamin A/C is a protein on the inner side of the nuclear membrane, and we then asked why lamin A/C can regulate the nuclear translocation of β-catenin. Previous studies have shown that emerin, a lamin-associated protein [ 23 ], can bind to β-catenin and inhibit its nuclear translocation [ 21 ]. We hypothesized that the decreased expression of lamin A/C in soft gel resulted in the diffusion of emerin in the cytoplasm, which restricts β-catenin entry into the nucleus.…”

Section: Resultsmentioning

confidence: 99%

Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses

Zhang

et al. 2023

Materials Today Bio

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Mesenchymal and induced pluripotent stem cell–based therapeutics: a comparison

Teale

Schneider

Eibl

et al. 2023

Appl Microbiol Biotechnol

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Stem cell–based cell therapeutics and especially those based on human mesenchymal stem cells (hMSCs) and induced pluripotent stem cells (hiPSCs) are said to have enormous developmental potential in the coming years. Their applications range from the treatment of orthopedic disorders and cardiovascular diseases to autoimmune diseases and even cancer. However, while more than 27 hMSC-derived therapeutics are currently commercially available, hiPSC-based therapeutics have yet to complete the regulatory approval process. Based on a review of the current commercially available hMSC-derived therapeutic products and upcoming hiPSC-derived products in phase 2 and 3, this paper compares the cell therapy manufacturing process between these two cell types. Moreover, the similarities as well as differences are highlighted and the resulting impact on the production process discussed. Here, emphasis is placed on (i) hMSC and hiPSC characteristics, safety, and ethical aspects, (ii) their morphology and process requirements, as well as (iii) their 2- and 3-dimensional cultivations in dependence of the applied culture medium and process mode. In doing so, also downstream processing aspects are covered and the role of single-use technology is discussed. Key points • Mesenchymal and induced pluripotent stem cells exhibit distinct behaviors during cultivation • Single-use stirred bioreactor systems are preferred for the cultivation of both cell types • Future research should adapt and modify downstream processes to available single-use devices

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Matrix remodeling controls a nuclear lamin A/C-emerin network that directs Wnt-regulated stem cell fate

Cited by 4 publications

References 59 publications

Nanotube patterning reduces macrophage inflammatory response via nuclear mechanotransduction

Nanotube patterning reduces macrophage inflammatory response via nuclear mechanotransduction

Chromatin remodeling and nucleoskeleton synergistically control osteogenic differentiation in different matrix stiffnesses

Mesenchymal and induced pluripotent stem cell–based therapeutics: a comparison

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