Wnt4 from the Niche Controls the Mechano-Properties and Quiescent State of Muscle Stem Cells

Eliazer, Susan; Muncie, Jonathon M.; Christensen, J. D.; Sun, Xinwei; D’Urso, Rebecca S.; Weaver, Valerie M.; Brack, Andrew S.

doi:10.1016/j.stem.2019.08.007

Cited by 127 publications

(135 citation statements)

References 75 publications

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“…Our results are comparable to mouse, where the density of MuSCs ranges from 5 to 20 cells/mm 2 ( Fig. 1 ) ( Parisi et al, 2015 ; Eliazer et al, 2019 ; Schaaf et al, 2018 ).…”

Section: Resultssupporting

confidence: 87%

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Isolation of muscle stem cells from rat skeletal muscles

et al. 2020

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Muscle stem cells (MuSCs) are involved in homeostatic maintenance of skeletal muscle and play a central role in muscle regeneration in response to injury. Thus, understanding MuSC autonomous properties is of fundamental importance for studies of muscle degenerative diseases and muscle plasticity. Rat, as an animal model, has been widely used in the skeletal muscle field, however rat MuSC isolation through fluorescence-activated cell sorting has never been described. This work validates a protocol for effective MuSC isolation from rat skeletal muscles. Tibialis anterior was harvested from female rats and digested for isolation of MuSCs. Three protocols, employing different cell surface markers (CD106, CD56, and CD29), were compared for their ability to isolate a highly enriched MuSC population. Cells isolated using only CD106 as a positive marker showed high expression of Pax7, ability to progress through myogenic lineage while in culture, and complete differentiation in serum-deprived conditions. The protocol was further validated in gastrocnemius, diaphragm, and the individual components of the pelvic floor muscle complex (coccygeus, iliocaudalis, and pubocaudalis), proving to be reproducible. CD106 is an efficient marker for reliable isolation of MuSCs from a variety of rat skeletal muscles.

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“…Our results are comparable to mouse, where the density of MuSCs ranges from 5 to 20 cells/mm 2 ( Fig. 1 ) ( Parisi et al, 2015 ; Eliazer et al, 2019 ; Schaaf et al, 2018 ).…”

Section: Resultssupporting

confidence: 87%

“…Our in situ evaluations ( Fig. 1 ) showed an average of 10 Pax7 + cells per mm 2 , which is also comparable to the number of MuSCs per mm 2 in mouse ( Parisi et al, 2015 ; Eliazer et al, 2019 ; Schaaf et al, 2018 ). Given the above and the larger size of the rat muscles, one can isolate a greater number of MuSCs from the rat.…”

Section: Discussionsupporting

confidence: 78%

Isolation of muscle stem cells from rat skeletal muscles

et al. 2020

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“…We verified the specificity of the coupled antibodies (listed in Table S3 ) by performing the corresponding isotypic controls ( Figure S2 A). In addition, we used fluorescence-activated cell sorting (FACS) to sort cells stained with these coupled antibodies and counterstained them with antibodies commonly used for immunofluorescence (IF) in the field ( Figures S2 B–S2D; Table S4 ) ( Eliazer et al., 2019 ; Machado et al., 2017 ; Paris et al., 2016 ). Finally, we confirmed that endogenous PAX7 expression analyzed with coupled anti-PAX7-AF647 antibody correlated with GFP expression in myogenic cells derived from Tg:PAX7-nGFP mouse muscles ( Figure S2 E).…”

Section: Resultsmentioning

confidence: 99%

Distinct Phases of Postnatal Skeletal Muscle Growth Govern the Progressive Establishment of Muscle Stem Cell Quiescence

et al. 2020

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Summary Muscle stem cells (or muscle satellite cells [MuSCs]) are required for postnatal growth. Yet, the detailed characterization of myogenic progression and establishment of quiescence during this process remains poorly documented. Here, we provide an overview of myogenic cells heterogeneity and dynamic from birth to adulthood using flow cytometry. We demonstrated that PAX7+ cells acquire an increasing ability to progress in the myogenic program from birth to adulthood. We then simultaneously analyzed the cycling state (KI67 expression) of the MuSCs and progenitors (PAX7+) and their progression into myogenic precursors (PAX7−MYOD+) and differentiating cells (MYOG+) in vivo . We identified two distinct peaks of myogenic differentiation between P7–P10 and P21–P28, and showed that the quiescent MuSC pool is established between 7 and 8 weeks of age. Overall our study provides a comprehensive in vivo characterization of myogenic heterogeneity and demonstrates the highly dynamic nature of skeletal muscle postnatal growth process.

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“…The modified β-catenin is now free to translocate to the nucleus, where it exerts its transcriptional activity and induces the expression of multiple Wnt ligands that feed forward to promote and reinforce mesoderm specification and gastrulation (Bienz, 2005;Chhabra et al, 2019;Kemp et al, 2005;Lindsley et al, 2006;Martyn et al, 2019;Laralynne Przybyla et al, 2016). Notably, Wnt/β-catenin signaling is conserved among model organisms and plays multiple roles throughout the course of embryogenesis and in adult stem cells (Clevers, 2006;Eliazer et al, 2019;Petersen and Reddien, 2009;van Amerongen and Nusse, 2009), implying that the tension-regulated activation of the pathway that we illustrate here is likely also conserved and re-used throughout development. In fact, Farge and colleagues demonstrated that the same Src-mediated phosphorylation at Y654 and subsequent release of junctional β-catenin occurs during mesoderm invagination in Drosophila embryos (Röper et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Mechanics regulate human embryonic stem cell self-organization to specify mesoderm

Muncie

Ayad

Lakins

et al. 2020

Preprint

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Embryogenesis is directed by morphogens that induce differentiation within a defined tissue geometry. Tissue organization is mediated by cell-cell and cell-extracellular matrix (ECM) adhesions and is modulated by cell tension and tissue-level force. Whether cell tension regulates development by directly influencing morphogen signaling remains unclear. Human embryonic stem cells (hESCs) exhibit an intrinsic capacity for self-organization that motivates their use as a tractable model of early human embryogenesis. We engineered patterned substrates that enhance cell-cell interactions to direct the self-organization of cultured hESCs into "gastrulation-like" nodes. Tissue geometries that generate local nodes of high cell-cell tension and induce these selforganized tissue nodes drive BMP4-dependent gastrulation by enhancing phosphorylation and nuclear translocation of β-catenin to promote Wnt signaling and mesoderm specification. The findings underscore the interplay between tissue organization, cell tension, and morphogendependent differentiation, and demonstrate that cell-and tissue-level forces directly regulate cell fate specification in early human development.

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Wnt4 from the Niche Controls the Mechano-Properties and Quiescent State of Muscle Stem Cells

Abstract: Highlights d Wnt4 from the muscle fiber maintains SC quiescence d Wnt4 activates Rho in QSCs to maintain their tension, shape, and niche retention d Rho represses YAP to prevent SC activation d Loss of myofiber-derived Wnt4 accelerates muscle regeneration after injury

Cited by 127 publications

References 75 publications

Isolation of muscle stem cells from rat skeletal muscles

Isolation of muscle stem cells from rat skeletal muscles

Distinct Phases of Postnatal Skeletal Muscle Growth Govern the Progressive Establishment of Muscle Stem Cell Quiescence

Mechanics regulate human embryonic stem cell self-organization to specify mesoderm

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