A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells

Xi, Haibin; Langerman, Justin; Sabri, Shan; Chien, Peggie; Young, Courtney S.; Younesi, Shahab; Hicks, Michael R.; Gonzalez, Karen M; Fujiwara, Wakana; Marzi, Julia; Liebscher, Simone; Spencer, Melissa J.; Handel, Ben Van; Evseenko, Denis; Schenke‐Layland, Katja; Plath, Kathrin; Pyle, April D.

doi:10.1016/j.stem.2020.04.017

Cited by 105 publications

(102 citation statements)

References 96 publications

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“…As previously published, whole hind limbs of developmental week 5–9 human embryos and fetuses (feet excluded for week 7.75–9), total hind limb skeletal muscles of week 12–18 human fetuses, and gastrocnemius or quadriceps muscles from juvenile and adult human subjects were digested into single cells. Dissociated cells were either sorted (fetal week 12 and above) to exclude the hematopoietic and endothelial lineages or directly used for downstream processing [ 39 ]. Figure 1 A shows single-cell ADNP transcriptomes of skeletal muscles, gastrocnemius, and quadriceps muscles from human specimen ranging from 5-week-gestation to 42 years of age.…”

Section: Resultsmentioning

confidence: 99%

“…The NCBI GEO website was screened for datasets derived from human single-cell transcriptomes of skeletal muscles. In the dataset GSE147457 [ 39 ] human tissues including hind limbs of developmental weeks 5–18 human embryos and fetuses, and gastrocnemius or quadriceps muscles from juvenile and adult human were processed into single cells. The UCSC Cell Browser [ 40 ] was used to analyze the data.…”

Section: Methodsmentioning

confidence: 99%

“…Chondro = Chondrocytes, Dermal = Dermal Fibroblasts Progenitors, EC = Endothelial Cells, EC-Hema = Endothelial, and Hematopoietic Cells, FAP = Fibro-adipogenic Progenitor, Hema = Hematopoietic Cells, Limb. Mesen = Limb Mesenchyme, MSC = Mesenchymal Stromal Cells, PreChondro = Pre-chondrocytes, RBC = Red Blood Cells, Schwann, SkM = Skeletal Muscle Cells, SMC = Smooth Muscle Cells, Teno = Tenocytes, WBC = White Blood Cells [ 39 ].…”

Section: Figurementioning

confidence: 99%

See 2 more Smart Citations

Single Cell ADNP Predictive of Human Muscle Disorders: Mouse Knockdown Results in Muscle Wasting

Kapitansky

Karmon

Sragovich

et al. 2020

Cells

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Activity-dependent neuroprotective protein (ADNP) mutations are linked with cognitive dysfunctions characterizing the autistic-like ADNP syndrome patients, who also suffer from delayed motor maturation. We thus hypothesized that ADNP is deregulated in versatile myopathies and that local ADNP muscle deficiency results in myopathy, treatable by the ADNP fragment NAP. Here, single-cell transcriptomics identified ADNP as a major constituent of the developing human muscle. ADNP transcript concentrations further predicted multiple human muscle diseases, with concentrations negatively correlated with the ADNP target interacting protein, microtubule end protein 1 (EB1). Reverting back to modeling at the single-cell level of the male mouse transcriptome, Adnp mRNA concentrations age-dependently correlated with motor disease as well as with sexual maturation gene transcripts, while Adnp expressing limb muscle cells significantly decreased with aging. Mouse Adnp heterozygous deficiency exhibited muscle microtubule reduction and myosin light chain (Myl2) deregulation coupled with motor dysfunction. CRISPR knockdown of adult gastrocnemius muscle Adnp in a Cas9 mouse resulted in treadmill (male) and gait (female) dysfunctions that were specifically ameliorated by treatment with the ADNP snippet, microtubule interacting, Myl2—regulating, NAP (CP201). Taken together, our studies provide new hope for personalized diagnosis/therapeutics in versatile myopathies.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Single Cell ADNP Predictive of Human Muscle Disorders: Mouse Knockdown Results in Muscle Wasting

Kapitansky

Karmon

Sragovich

et al. 2020

Cells

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“…Of note, a recent study also showed that PDGF-BB promotes migration of various types of muscle interstitial cells via interaction with its putative receptor, platelet-derived growth factor receptor-b (PDGFR-b) (Camps et al, 2019). As this phenomenon occurs during embryonic development (Cappellari et al, 2013), translating this approach to iPSC-derived myogenic progenitors may result in greater cell transmigration than what observed with adult myoblasts, given the embryonic-/foetal-like identity of most currently available skeletal myogenic iPSC derivatives (Xi et al, 2020).…”

Section: Modulating Migration: Systemic Deliverymentioning

confidence: 99%

Cellular dynamics of myogenic cell migration: molecular mechanisms and implications for skeletal muscle cell therapies

2020

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Directional cell migration is a critical process underlying morphogenesis and post-natal tissue regeneration. During embryonic myogenesis, migration of skeletal myogenic progenitors is essential to generate the anlagen of limbs, diaphragm and tongue, whereas in post-natal skeletal muscles, migration of muscle satellite (stem) cells towards regions of injury is necessary for repair and regeneration of muscle fibres. Additionally, safe and efficient migration of transplanted cells is critical in cell therapies, both allogeneic and autologous. Although various myogenic cell types have been administered intramuscularly or intravascularly, functional restoration has not been achieved yet in patients with degenerative diseases affecting multiple large muscles. One of the key reasons for this negative outcome is the limited migration of donor cells, which hinders the overall cell engraftment potential. Here, we review mechanisms of myogenic stem/progenitor cell migration during skeletal muscle development and post-natal regeneration. Furthermore, strategies utilised to improve migratory capacity of myogenic cells are examined in order to identify potential treatments that may be applied to future transplantation protocols.

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“…Here, we describe a novel method which significantly increases myofiber maturation over existing protocols. While current strategies can result in differentiation of myogenic cells up to the embryonic to fetal transition (Al Xi et al, 2020), our improved method results in well-organized myofibers with significant activation of the fast myosin IIa (MYH1), IIx (MYH2) and IIb (MYH4), which are respectively first expressed during fetal, late fetal, and early post-natal stages (Schiaffino et al, 2015). While most of DMD pathological landmarks have been defined during post-natal stages, the primary events leading to these defects likely happen during fetal development.…”

Section: Discussionmentioning

confidence: 99%

Prednisolone rescues Duchenne Muscular Dystrophy phenotypes in human pluripotent stem cells-derived skeletal muscle in vitro

Tanoury

Zimmerman

Rao

et al. 2020

Preprint

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Duchenne Muscular Dystrophy (DMD) is a devastating genetic disease leading to degeneration of skeletal muscles and premature death. How dystrophin absence leads to muscle wasting remains unclear. Here, we describe an optimized protocol to differentiate human induced Pluripotent Stem Cells (iPSC) to a late myogenic stage. This allows to recapitulate classical DMD phenotypes (mislocalization of proteins of the Dystrophin-glycoprotein associated complex (DGC), increased fusion, myofiber branching, force contraction defects and calcium hyperactivation) in isogenic DMD-mutant iPSC lines in vitro. Treatment of the myogenic cultures with prednisolone (the standard of care for DMD) can dramatically rescue force contraction, fusion and branching defects in DMD iPSC lines. This argues that prednisolone acts directly on myofibers, challenging the largely prevalent view that its beneficial effects are due to anti-inflammatory properties. Our work introduces a new human in vitro model to study the onset of DMD pathology and test novel therapeutic approaches.

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A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells

Cited by 105 publications

References 96 publications

Single Cell ADNP Predictive of Human Muscle Disorders: Mouse Knockdown Results in Muscle Wasting

Single Cell ADNP Predictive of Human Muscle Disorders: Mouse Knockdown Results in Muscle Wasting

Cellular dynamics of myogenic cell migration: molecular mechanisms and implications for skeletal muscle cell therapies

Prednisolone rescues Duchenne Muscular Dystrophy phenotypes in human pluripotent stem cells-derived skeletal muscle in vitro

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