scholarly journals Arsenic Directs Stem Cell Fate by Imparting Notch Signaling Into the Extracellular Matrix Niche

2020 ◽  
Vol 177 (2) ◽  
pp. 494-505
Author(s):  
Teresa Anguiano ◽  
Amrita Sahu ◽  
Baoli Qian ◽  
Wan-Yee Tang ◽  
Fabrisia Ambrosio ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Cell Fate ◽  
Disease Risk ◽  
Myogenic Differentiation ◽  
Muscle Metabolism ◽  
Muscle Stem Cells ◽  
Skeletal Muscle Dysfunction ◽  
Cell Niche

Abstract Compromise of skeletal muscle metabolism and composition may underlie the etiology of cardiovascular and metabolic disease risk from environmental arsenic exposures. We reported that arsenic impairs muscle maintenance and regeneration by inducing maladaptive mitochondrial phenotypes in muscle stem cells (MuSC), connective tissue fibroblasts (CTF), and myofibers. We also found that arsenic imparts a dysfunctional memory in the extracellular matrix (ECM) that disrupts the MuSC niche and is sufficient to favor the expansion and differentiation of fibrogenic MuSC subpopulations. To investigate the signaling mechanisms involved in imparting a dysfunctional ECM, we isolated skeletal muscle tissue and CTF from mice exposed to 0 or 100 μg/l arsenic in their drinking water for 5 weeks. ECM elaborated by arsenic-exposed CTF decreased myogenesis and increased fibrogenic/adipogenic MuSC subpopulations and differentiation. However, treating arsenic-exposed mice with SS-31, a mitochondrially targeted peptide that repairs the respiratory chain, reversed the arsenic-promoted CTF phenotype to one that elaborated an ECM supporting normal myogenic differentiation. SS-31 treatment also reversed arsenic-induced Notch1 expression, resulting in an improved muscle regeneration after injury. We found that persistent arsenic-induced CTF Notch1 expression caused the elaboration of dysfunctional ECM with increased expression of the Notch ligand DLL4. This DLL4 in the ECM was responsible for misdirecting MuSC myogenic differentiation. These data indicate that arsenic impairs muscle maintenance and regenerative capacity by targeting CTF mitochondria and mitochondrially directed expression of dysfunctional regulators in the stem cell niche. Therapies that restore muscle cell mitochondria may effectively treat arsenic-induced skeletal muscle dysfunction and compositional decline.

scholarly journals The transcription factor NF-Y participates to stem cell fate decision and regeneration in adult skeletal muscle

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Giovanna Rigillo ◽  
Valentina Basile ◽  
Silvia Belluti ◽  
Mirko Ronzio ◽  
Elisabetta Sauta ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Transcription Factor ◽  
Stem Cell ◽  
Satellite Cells ◽  
Cell Biology ◽  
Myogenic Differentiation ◽  
Stem Cell Population ◽  
Adult Skeletal Muscle ◽  
Muscle Stem Cells

AbstractThe transcription factor NF-Y promotes cell proliferation and its activity often declines during differentiation through the regulation of NF-YA, the DNA binding subunit of the complex. In stem cell compartments, the shorter NF-YA splice variant is abundantly expressed and sustains their expansion. Here, we report that satellite cells, the stem cell population of adult skeletal muscle necessary for its growth and regeneration, express uniquely the longer NF-YA isoform, majorly associated with cell differentiation. Through the generation of a conditional knock out mouse model that selectively deletes the NF-YA gene in satellite cells, we demonstrate that NF-YA expression is fundamental to preserve the pool of muscle stem cells and ensures robust regenerative response to muscle injury. In vivo and ex vivo, satellite cells that survive to NF-YA loss exit the quiescence and are rapidly committed to early differentiation, despite delayed in the progression towards later states. In vitro results demonstrate that NF-YA-depleted muscle stem cells accumulate DNA damage and cannot properly differentiate. These data highlight a new scenario in stem cell biology for NF-Y activity, which is required for efficient myogenic differentiation.

scholarly journals Mechanical Compression Creates a Quiescent Muscle Stem Cell Niche

2021 ◽  
Author(s):  
Jiaxiang Tao ◽  
Mohammad Ikbal Choudhury ◽  
Debonil Maity ◽  
Taeki Kim ◽  
Sean Sun ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Fate ◽  
Life Time ◽  
Apical Surface ◽  
Muscle Stem Cells ◽  
Cell Niche ◽  
Edge Tension ◽  
Stem Cell State

Skeletal muscles can regenerate throughout life time from resident Pax7-expressing (Pax7+) muscle stem cells (MuSCs). Pax7+ MuSCs are normally quiescent and localized at a niche in which they are attached to the extracellular matrix basally and compressed against the myofiber apically. Upon muscle injury, MuSCs lose apical contact with the myofiber and re-enter cell cycle to initiate regeneration. Prior studies on the physical niche of MuSCs focused on basal elasticity, and significance of the apical force exerted on MuSCs remains unaddressed. Here we simulate MuSCs' mechanical environment in vivo by applying physical compression to MuSCs' apical surface. We demonstrate that compression drives activated MuSCs back to a quiescent stem cell state, even when seeded on different basal elasticities. By mathematical modeling and manipulating cell tension, we conclude that low overall tension combined with high edge tension generated by compression lead to MuSC quiescence. We further show that apical compression results in up-regulation of Notch downstream genes, accompanied by increased levels of nuclear Notch. The compression-induced nuclear Notch is ligand-independent, as it does not require the canonical S2-cleavage of Notch by ADAM10/17. Our results fill the knowledge gap on the role of apical tension for MuSC fate. Implications to how stem cell fate and activity are interlocked with the mechanical integrity of its resident tissue are discussed.

scholarly journals Skeletal Muscle Stem Cell Niche from Birth to Old Age

2020 ◽  
Author(s):  
Madalina-Gabriela Barbu ◽  
Andreea-Elena Boboc ◽  
Lidia Filip ◽  
Oana-Larisa Bugnar ◽  
Dragos Cretoiu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Satellite Cells ◽  
Stem Cell Niche ◽  
Myogenic Differentiation ◽  
Cell Types ◽  
Undifferentiated Cells ◽  
Cell Niche ◽  
Therapeutic Tools

Stem cells are defined as undifferentiated cells that are able to unlimitedly renew themselves within controlled conditions and to differentiate into a multitude of mature cell types. Skeletal muscle stem cells, represented predominantly by satellite cells, show a variable capability of self-renewal and myogenic differentiation. They were found to be involved not only in the growth of myofibers during neonatal and juvenile life but also in the regeneration of skeletal muscles after an injury. The microenvironment in which stem cells are nourished and maintained dormant preceding division and differentiation is known as “niche.” The niche consists of myofibers, which are believed to modulate the active/inactive state of the stem cells, extracellular matrix, neural networks, blood vessels, and a multitude of soluble molecules. It was observed that changes in the composition of the niche have an impact on the stem cell functions and hierarchy. Furthermore, it seems that its layout is variable throughout the entire life, translating into a decrease in the regenerative capacity of satellite cells in aged tissues. The scope of this chapter is to provide a detailed view of the changes that occur in the skeletal stem cell niche during life and to analyze their implications on tissue regeneration. Future studies should focus on developing new therapeutic tools for diseases involving muscle atrophy.

Stem Cell Function, Self-Renewal, Heterogeneity, and Regenerative Potential in Skeletal Muscle Stem Cells

2012 ◽  
Vol 2 (1) ◽  
pp. 11-21
Author(s):  
Silvia Cristini ◽  
Giulio Alessandri ◽  
Francesco Acerbi ◽  
Daniela Tavian ◽  
Eugenio A. Parati ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Self Renewal ◽  
Muscle Stem Cells ◽  
Skeletal Muscle Stem Cells

Stem Cell Function, Self-Renewal, Heterogeneity, and Regenerative Potential in Skeletal Muscle Stem Cells

2012 ◽  
Vol 2 (1) ◽  
pp. 11-21
Author(s):  
Silvia Cristini ◽  
Giulio Alessandri ◽  
Francesco Acerbi ◽  
Daniela Tavian ◽  
Eugenio A. Parati ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Function ◽  
Self Renewal ◽  
Muscle Stem Cells ◽  
Skeletal Muscle Stem Cells

scholarly journals Extracellular matrix and the neural stem cell niche

2011 ◽  
Vol 71 (11) ◽  
pp. 1006-1017 ◽  
Author(s):  
Ilias Kazanis ◽  
Charles ffrench-Constant
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Neural Stem Cell ◽  
Stem Cell Niche ◽  
Neural Stem Cell Niche ◽  
Cell Niche

scholarly journals Hormonal Regulation of Stem Cell Proliferation at the Arabidopsis thaliana Root Stem Cell Niche

2021 ◽  
Vol 12 ◽  
Author(s):  
Mónica L. García-Gómez ◽  
Adriana Garay-Arroyo ◽  
Berenice García-Ponce ◽  
María de la Paz Sánchez ◽  
Elena R. Álvarez-Buylla
Keyword(s):  
Cell Proliferation ◽  
Arabidopsis Thaliana ◽  
Stem Cell ◽  
Cell Fate ◽  
Regulatory Network ◽  
Hormonal Regulation ◽  
Stem Cell Niche ◽  
Quiescent Center ◽  
Root Stem Cell ◽  
Cell Niche

The root stem cell niche (SCN) of Arabidopsis thaliana consists of the quiescent center (QC) cells and the surrounding initial stem cells that produce progeny to replenish all the tissues of the root. The QC cells divide rather slowly relative to the initials, yet most root tissues can be formed from these cells, depending on the requirements of the plant. Hormones are fundamental cues that link such needs with the cell proliferation and differentiation dynamics at the root SCN. Nonetheless, the crosstalk between hormone signaling and the mechanisms that regulate developmental adjustments is still not fully understood. Developmental transcriptional regulatory networks modulate hormone biosynthesis, metabolism, and signaling, and conversely, hormonal responses can affect the expression of transcription factors involved in the spatiotemporal patterning at the root SCN. Hence, a complex genetic–hormonal regulatory network underlies root patterning, growth, and plasticity in response to changing environmental conditions. In this review, we summarize the scientific literature regarding the role of hormones in the regulation of QC cell proliferation and discuss how hormonal signaling pathways may be integrated with the gene regulatory network that underlies cell fate in the root SCN. The conceptual framework we present aims to contribute to the understanding of the mechanisms by which hormonal pathways act as integrators of environmental cues to impact on SCN activity.

scholarly journals Boron induces osteogenesis by stimulating NaBC1 in cooperation with BMPR1A

2020 ◽  
Author(s):  
Patricia Rico ◽  
Aleixandre Rodrigo-Navarro ◽  
Laura Sánchez Pérez ◽  
Manuel Salmeron-Sanchez
Keyword(s):  
Stem Cell ◽  
Ion Channel ◽  
Cell Fate ◽  
Cell Metabolism ◽  
Cost Effective ◽  
Material System ◽  
Mechanosensitive Ion Channel ◽  
The Media ◽  
Cell Niche ◽  
System Approaches

AbstractThe intrinsic properties of Mesenchymal Stem Cells (MSCs) make them ideal candidates for tissue engineering applications as they are regulated by the different signals present in the stem cell niche. Considerable efforts have been made to control stem cell behavior by designing material system approaches to engineer synthetic extracellular matrices and/or include soluble factors in the media. This work proposes a novel and simple approach based on ion-channel stimulation to determine stem cell fate that avoids the use of growth factors (GFs). We used boron ion - essential item in cell metabolism - transported inside cells by the NaBC1-channel. Addition of boron alone enhanced MSC adhesion and contractility, promoted osteogenesis and inhibited adipogenesis. The stimulated NaBC1 promoted osteogenesis via activation of the BMP canonical pathway (comprising Smad1 and YAP nucleus translocation and osteopontin expression) through a mechanism that involves simultaneous NaBC1/BMPR1A and NaBC1/α5β1/αvβ3 co-localization,. We describe a novel function for NaBC1 as a mechanosensitive ion-channel capable of interacting and stimulating GF receptors and fibronectin-binding integrins. Our results open up new biomaterial engineering approaches for biomedical applications by a cost-effective strategy that avoids the use of soluble GFs.

Sign in / Sign up

Export Citation Format

Share Document