The mini-IDLE 3D biomimetic culture assay enables interrogation of mechanisms governing muscle stem cell quiescence and niche repopulation DOI Creative Commons

Erik Jacques,

Yinni Kuang,

Allison P Kann

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Dec. 20, 2022

Adult skeletal muscle harbours a population of stem cells (MuSCs) that are required for repair after tissue injury. In youth, MuSCs return to reversible state cell-cycle arrest termed ‘quiescence’ injury resolution. Conversely, some in aged remain semi-activated, causing premature response injuries results incomplete and eventual cell depletion. Regulating this balance between MuSC quiescence activation may hold the key restoring homeostasis with age, but is incompletely understood. To fill gap, we developed simple tractable vitro method, rapidly inactivate freshly isolated from young murine muscle, them quiescent-like at least 1-week, which name mini-IDLE ( I nactivation D ormancy LE veraged vitro). This was achieved by introducing into 3D bioartificial niche comprised thin sheet mouse myotubes, demonstrate provides minimal cues necessary induce quiescence. With different starting numbers MuSCs, assay revealed cellular heterogeneity population-level adaptations converged on common repopulation density; behaviours previously observed only vivo. Quiescence-associated hallmarks included Pax7 + CalcR DDX6 MyoD - c-FOS signature, morphologies, polarized markers. Leveraging high-content bioimaging pipelines, relationship morphology fate signatures possible real-time morphology-based screening. When using they displayed aberrant proliferative activities delayed inactivation kinetics, among other quiescence-associated defects show partially rescued wortmannin treatment. Thus, offers an unprecedented opportunity systematically investigate long-standing queries areas such as regulation pool size functional within population, uncover regulators youth age.

Language: Английский

Duchenne muscular dystrophy: disease mechanism and therapeutic strategies DOI Creative Commons
Addeli Bez Batti Angulski,

Nora Hosny,

Houda Cohen

et al.

Frontiers in Physiology, Journal Year: 2023, Volume and Issue: 14

Published: June 26, 2023

Duchenne muscular dystrophy (DMD) is a severe, progressive, and ultimately fatal disease of skeletal muscle wasting, respiratory insufficiency, cardiomyopathy. The identification the dystrophin gene as central to DMD pathogenesis has led understanding membrane proteins involved in stability focal point disease. lessons learned from decades research human genetics, biochemistry, physiology have culminated establishing myriad functionalities striated biology. Here, we review pathophysiological basis discuss recent progress toward development therapeutic strategies for that are currently close or clinical trials. first section focuses on mechanisms contributing instability, inflammation, fibrosis. second discusses used treat DMD. This includes focus outlining strengths limitations approaches directed at correcting genetic defect through replacement, modification, repair, and/or range dystrophin-independent approaches. final highlights different

Language: Английский

Citations

71
Mechanisms of mechanotransduction and physiological roles of PIEZO channels DOI
Bailong Xiao

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

Language: Английский

Citations

39
Three-dimensional imaging studies in mice identify cellular dynamics of skeletal muscle regeneration DOI

Brittany C. Collins,

Jacob B. Shapiro, Mya M. Scheib

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: 59(11), P. 1457 - 1474.e5

Published: April 2, 2024

Language: Английский

Citations

21
The emergence of the stem cell niche DOI Creative Commons
Michael R. Hicks, April D. Pyle

Trends in Cell Biology, Journal Year: 2022, Volume and Issue: 33(2), P. 112 - 123

Published: Aug. 4, 2022

Niches coevolve with the maturation of progenitor and stem cells from development through to adulthood.Fetal progenitors in emerging niches are highly expansive, whereas adult regulate cell quiescence.Fetal less able occupy during transplantation.Niche formation is stepwise, involving cell–cell contact, followed by cell–extracellular matrix affect polarity maturation.Emerging use similar pathways mechanisms regeneration.Understanding niche may improve quality quantity within niches.Supportive types different homeostatic niches.Human pluripotent lineages can be used model components vitro vivo. Stem composed dynamic microenvironments that support over a lifetime. The distinct because its main role build organ systems development. Emerging mature stages form enable proper support. As niches, this review highlights how differences skeletal muscle microenvironment influence versus satellite (SC) muscle, which among most regenerative tissue systems. We contrast intrinsic properties between throughout adulthood. describe new applications for generating human (hPSCs) using developmental principles highlight potential regeneration therapeutics.

Language: Английский

Citations

60
An injury-responsive Rac-to-Rho GTPase switch drives activation of muscle stem cells through rapid cytoskeletal remodeling DOI Creative Commons
Allison P Kann, Margaret Hung, Wei Wang

et al.

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(6), P. 933 - 947.e6

Published: May 20, 2022

Language: Английский

Citations

58
Membrane curvature governs the distribution of Piezo1 in live cells DOI Creative Commons
Shilong Yang,

Xinwen Miao,

Steven E. Arnold

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Dec. 3, 2022

Piezo1 is a bona fide mechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of within cell essential for various biological processes including cytokinesis, migration, and wound healing. However, the underlying principles that guide subcellular remain largely unexplored. Here, we demonstrate membrane curvature serves as key regulator spatial plasma living depletes from highly curved protrusions such filopodia enriches to nanoscale invaginations. Quantification curvature-dependent sorting directly reveals situ nano-geometry Piezo1-membrane complex. density on increases upon activation, independent calcium, suggesting flattening opening. Consequently, expression inhibits formation, an effect diminishes with activation.

Language: Английский

Citations

51
The role of PIEZO ion channels in the musculoskeletal system DOI
Alireza Savadipour, D. Palmer, Erica V. Ely

et al.

AJP Cell Physiology, Journal Year: 2023, Volume and Issue: 324(3), P. C728 - C740

Published: Jan. 31, 2023

PIEZO1 and PIEZO2 are mechanosensitive cation channels that highly expressed in numerous tissues throughout the body exhibit diverse, cell-specific functions multiple organ systems. Within musculoskeletal system, to maintain muscle bone mass, sense tendon stretch, regulate senescence apoptosis response mechanical stimuli within cartilage intervertebral disc. is essential for transducing pain touch sensations as well proprioception nervous which can affect health. have been shown act both independently synergistically different cell types. Conditions alter PIEZO channel mechanosensitivity, such inflammation or genetic mutations, drastic effects on these functions. For this reason, therapeutic approaches PIEZO-related disease focus altering and/or activity a controlled manner, either through inhibition with small molecules, dietary control supplementation healthy membrane composition. Although many opportunities better understand remain, studies summarized review highlight how crucial health point promising possible avenues their modulation target.

Language: Английский

Citations

37
Lepr‐Expressing PDLSCs Contribute to Periodontal Homeostasis and Respond to Mechanical Force by Piezo1 DOI Creative Commons
Danting Zhang, Weimin Lin, Shuang Jiang

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(29)

Published: Aug. 8, 2023

Periodontium supports teeth in a mechanically stimulated tissue environment, where heterogenous stem/progenitor populations contribute to periodontal homeostasis. In this study, Leptin receptor+ (Lepr+) cells are identified as distinct ligament stem cell (PDLSC) population by single-cell RNA sequencing and lineage tracing. These Lepr+ PDLSCs located the peri-vascular niche, possessing multilineage potential contributing repair response injury. Ablation of disrupts Hyper-loading unloading occlusal forces modulate activation. Piezo1 is demonstrated that mediates mechanosensing conditional Piezo1-deficient mice. Meanwhile, Yoda1, selective activator Piezo1, significantly accelerates growth via induction cells. summary, Lepr marks unique multipotent PDLSC vivo, toward homeostasis Piezo1-mediated mechanosensing.

Language: Английский

Citations

33
PIEZO1 loss-of-function compound heterozygous mutations in the rare congenital human disorder Prune Belly Syndrome DOI Creative Commons
Nathália G. Amado, E. D. Nosyreva, David R. Thompson

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 6, 2024

Prune belly syndrome (PBS), also known as Eagle-Barret syndrome, is a rare, multi-system congenital myopathy primarily affecting males. Phenotypically, PBS cases manifest three cardinal pathological features: urinary tract dilation with poorly contractile smooth muscle, wrinkled flaccid ventral abdominal wall skeletal muscle deficiency, and intra-abdominal undescended testes. Genetically, understood. After performing whole exome sequencing in patients, we identify one compound heterozygous variant the PIEZO1 gene. cation-selective channel activated by various mechanical forces widely expressed throughout lower tract. Here conduct an extensive functional analysis of variants that reveal loss-of-function characteristics pressure-induced normalized open probability (NPo) channel, while no change observed single-channel currents. Furthermore, Yoda1, activator, can rescue NPo defect mutant channels. Thus, mutations may be causal for vitro cellular pathophysiological phenotype could rescued small molecule, Yoda1. Activation might provide promising means treating other related bladder dysfunctional states.

Language: Английский

Citations

13
Piezo1 and its inhibitors: Overview and perspectives DOI Creative Commons

Nguyen Duc Thien,

Nguyen Hai-Nam,

Duong Tien Anh

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 273, P. 116502 - 116502

Published: May 14, 2024

The cation channel Piezo1, a crucial mechanotransducer found in various organs and tissues, has gained considerable attention as therapeutic target recent years. Following this trend, several Piezo1 inhibitors have been discovered studied for potential pharmacological properties. This review provides an overview of the structural functional importance well discussing biological activities based on their mechanism action. compounds addressed include toxin GsMTx4, Aβ peptides, certain fatty acids, ruthenium red gadolinium, Dooku1, natural products tubeimoside I, salvianolic acid B, jatrorrhzine, escin. findings revealed that misexpression can be associated with number chronic diseases, including hypertension, cancer, hemolytic anemia. Consequently, inhibiting subsequent calcium influx beneficial effects pathological processes, shown by many vitro vivo studies. However, development is still its beginnings, opportunities challenges remaining to explored.

Language: Английский

Citations

13