Skeletal Muscle Stem Cell Niche from Birth to Old Age

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.

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Stem cell niche signals Wnt, Hedgehog, and Notch distinctively regulate Drosophila follicle precursor cell differentiation

10.1101/114090 ◽

2017 ◽

Author(s):

Wei Dai ◽

Amy Peterson ◽

Thomas Kenney ◽

Denise J. Montell

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Progenitor Cells ◽

Cell Fate ◽

Stem Cell Niche ◽

Adult Stem Cells ◽

Cell Types ◽

Wnt Signalling ◽

Main Body ◽

Cell Niche

AbstractAdult stem cells commonly give rise to transit-amplifying progenitors, whose progeny differentiate into distinct cell types. Signals within the stem cell niche maintain the undifferentiated state. However it is unclear whether or how niche signals might also coordinate fate decisions within the progenitor pool. Here we use quantitative microscopy to elucidate distinct roles for Wnt, Hedgehog (Hh), and Notch signalling in progenitor development in the Drosophila ovary. Follicle stem cells (FSCs) self-renew and produce precursors whose progeny adopt distinct polar, stalk, and main body cell fates. We show that a steep gradient of Wnt signalling maintains a multipotent state in proximally located progenitor cells by inhibiting expression of the cell fate determinant Eyes Absent (Eya). A shallower gradient of Hh signalling controls the proliferation to differentiation transition. The combination of Notch and Wnt signalling specifies polar cells. These findings reveal a mechanism by which multiple niche signals coordinate cell fate diversification of progenitor cells.

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

Nature Communications ◽

10.1038/s41467-021-26293-w ◽

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.

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Influence of exercise and aging on extracellular matrix composition in the skeletal muscle stem cell niche

Journal of Applied Physiology ◽

10.1152/japplphysiol.00594.2016 ◽

2016 ◽

Vol 121 (5) ◽

pp. 1053-1058 ◽

Cited By ~ 36

Author(s):

Koyal Garg ◽

Marni D. Boppart

Keyword(s):

Skeletal Muscle ◽

Stem Cell ◽

Satellite Cells ◽

Stem Cell Niche ◽

Cell Function ◽

Skeletal Muscle Regeneration ◽

Matrix Composition ◽

Muscle Stem Cell ◽

Cell Niche ◽

Exercise And Aging

Skeletal muscle is endowed with a remarkable capacity for regeneration, primarily due to the reserve pool of muscle resident satellite cells. The satellite cell is the physiologically quiescent muscle stem cell that resides beneath the basal lamina and adjacent to the sarcolemma. The anatomic location of satellite cells is in close proximity to vasculature where they interact with other muscle resident stem/stromal cells (e.g., mesenchymal stem cells and pericytes) through paracrine mechanisms. This mini-review describes the components of the muscle stem cell niche, as well as the influence of exercise and aging on the muscle stem cell niche. Although exercise promotes ECM reorganization and stem cell accumulation, aging is associated with dense ECM deposition and loss of stem cell function resulting in reduced regenerative capacity and strength. An improved understanding of the niche elements will be valuable to inform the development of therapeutic interventions aimed at improving skeletal muscle regeneration and adaptation over the life span.

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Unsupervised cell interaction profiling reveals major architectural differences between small intestinal and colonic epithelial crypts

10.1101/2020.03.06.980243 ◽

2020 ◽

Author(s):

Jason T. Serviss ◽

Nathanael Andrews ◽

Agneta B. Andersson ◽

Ewa Dzwonkowska ◽

Rosan Heijboer ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Niche ◽

Paneth Cell ◽

Cell Types ◽

Cell Interaction ◽

Colonic Epithelium ◽

Cellular Interactions ◽

Small Intestinal ◽

Cell Niche

AbstractCellular identity in complex multicellular organisms is strictly maintained over the course of life. This control is achieved in part by the organ structure itself, such that neighboring cells influence each other’s identity. However, large-scale investigation of the cellular interactome has been technically challenging. Here, we develop CIM-seq, an unsupervised and high-throughput method to analyze direct physical cell-cell interactions between every cell type in a given tissue. CIM-seq is based on RNA sequencing of incompletely dissociated cells, followed by computational deconvolution of these into their constituent cell types using machine learning. We use CIM-seq to define the cell interaction landscape of the mouse small intestinal and colonic epithelium, uncovering both known and novel interactions. Specifically, we find that the general architecture of the stem cell niche is radically different between the two tissues. In small intestine, the stem-Paneth cell interaction forms an exceptionally strong and exclusive niche, in which Paneth cells provide Wnt ligands1. In colonic epithelium, no similar compartment exists to support stem cells, and Wnt signaling is provided by a mesenchymal cell layer2,3. However, colonic stem cells are supported by an adjacent, previously unrecognized goblet cell subtype expressing the wound-healing marker Plet1, which is also highly upregulated during regeneration of colon epithelium. These results identify novel cellular interactions specific for the colonic stem cell niche and suggest an additional level of structural control in the colon. CIM-seq is broadly applicable to studies that aim to simultaneously investigate the constituent cell types and the global interaction profile in a specific tissue.

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Satellite Cells and the Muscle Stem Cell Niche

Physiological Reviews ◽

10.1152/physrev.00043.2011 ◽

2013 ◽

Vol 93 (1) ◽

pp. 23-67 ◽

Cited By ~ 834

Author(s):

Hang Yin ◽

Feodor Price ◽

Michael A. Rudnicki

Keyword(s):

Skeletal Muscle ◽

Stem Cell ◽

Satellite Cells ◽

Muscle Regeneration ◽

Stem Cell Niche ◽

Skeletal Muscle Regeneration ◽

Stem Cell Population ◽

Muscle Stem Cell ◽

Adult Skeletal Muscle ◽

Cell Niche

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration.

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Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche

Annual Review of Biomedical Engineering ◽

10.1146/annurev-bioeng-062117-120954 ◽

2018 ◽

Vol 20 (1) ◽

pp. 21-47 ◽

Cited By ~ 35

Author(s):

Christopher M. Madl ◽

Sarah C. Heilshorn

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Stem Cell Niche ◽

Disease Modeling ◽

Cell Types ◽

Patient Specific ◽

Matrix Mechanics ◽

Culture Models ◽

Cell Niche

Stem cells are a powerful resource for many applications including regenerative medicine, patient-specific disease modeling, and toxicology screening. However, eliciting the desired behavior from stem cells, such as expansion in a naïve state or differentiation into a particular mature lineage, remains challenging. Drawing inspiration from the native stem cell niche, hydrogel platforms have been developed to regulate stem cell fate by controlling microenvironmental parameters including matrix mechanics, degradability, cell-adhesive ligand presentation, local microstructure, and cell–cell interactions. We survey techniques for modulating hydrogel properties and review the effects of microenvironmental parameters on maintaining stemness and controlling differentiation for a variety of stem cell types. Looking forward, we envision future hydrogel designs spanning a spectrum of complexity, ranging from simple, fully defined materials for industrial expansion of stem cells to complex, biomimetic systems for organotypic cell culture models.

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