Identification and Characterization of the Dermal Panniculus Carnosus Muscle Stem Cells

Naldaiz-Gastesi, Neia; Goicoechea, Maria; Alonso-Martín, Sonia; Aiastui, Ana; López-Mayorga, Macarena; García-Belda, Paula; Lacalle, J; José, Carlos San; Araúzo-Bravo, Marcos J.; Trouilh, Lidwine; Leberre, Véronique Anton; Herrero, Diego; Matheu, Ander; Bernad, António; García‐Verdugo, José Manuel; Carvajal, Jaime J.; Relaix, Frédéric; Munáin, Adolfo López de; García-Parra, Patricia; Izeta, Ander

doi:10.1016/j.stemcr.2016.08.002

Cited by 34 publications

(44 citation statements)

References 60 publications

(77 reference statements)

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“…S3 A-C). The panniculus carnosus is a sheet of muscle cells underneath the mouse back skin dermis; it is vestigial or absent in human skin (31). To circumvent this problem, we switched to newborn mouse tail skin, which has a thick epidermis and no panniculus carnosus, similar to human skin.…”

Section: Resultsmentioning

confidence: 99%

484 Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model

Lü

et al. 2017

Journal of Investigative Dermatology

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The prokaryotic CRISPR/Cas9 system has recently emerged as a powerful tool for genome editing in mammalian cells with the potential to bring curative therapies to patients with genetic diseases. However, efficient in vivo delivery of this genome editing machinery and indeed the very feasibility of using these techniques in vivo remain challenging for most tissue types. Here, we show that nonreplicable Cas9/sgRNA ribonucleoproteins can be used to correct genetic defects in skin stem cells of postnatal recessive dystrophic epidermolysis bullosa (RDEB) mice. We developed a method to locally deliver Cas9/sgRNA ribonucleoproteins into the skin of postnatal mice. This method results in rapid gene editing in epidermal stem cells. Using this method, we show that Cas9/sgRNA ribonucleoproteins efficiently excise exon80, which covers the point mutation in our RDEB mouse model, and thus restores the correct localization of the collagen VII protein in vivo. The skin blistering phenotype is also significantly ameliorated after treatment. This study provides an in vivo gene correction strategy using ribonucleoproteins as curative treatment for genetic diseases in skin and potentially in other somatic tissues.in vivo gene editing | Cas9/sgRNA ribonucleoproteins | skin stem cell | electroporation | RDEB C RISPR/Cas9-mediated genome editing has recently emerged as a powerful tool for genome engineering and for use as a potential therapeutic method to treat patients with genetic diseases (1-3). CRISPR/Cas9-mediated somatic genome editing of multiple mice organs, including lung, liver, brain, pancreas, and muscle, have been reported (4-10). To date, most approaches have relied on virus-based delivery systems, which have drawbacks such as potential integration of viral DNA into a host genome, off-target effects due to prolonged expression of genome editing machinery, and possible activation of virus-triggered host immune responses. Additionally, most therapeutic applications will require the tissue-specific delivery of the genome editing machinery in vivo. So far, this has remained challenging for most tissues, such as skin.In healthy skin, epidermal keratinocytes and dermal fibroblasts secrete collagen VII protein and it in turn forms stable homotrimers to assemble into networks of anchoring fibrils (11,12). The anchoring fibrils are located within the basement membrane zone (BMZ) between the epidermis and dermis, where they participate in stabilizing the association of the epidermis to the underlying dermis (13). In patients with recessive dystrophic epidermolysis bullosa (RDEB), mutations in the Col7a1 gene cause absent or dysfunctional collagen VII protein production, which leads to defective epidermal-dermal adhesion (14). The main clinical manifestations of RDEB include: chronic and severe cutaneous blistering, especially on hands and feet; damage to internal epithelia, such as oral, esophageal, and anal structures; an increased risk for developing aggressive forms of squamous cell carcinoma; and overall reduced life expectanc...

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Section: Resultsmentioning

confidence: 99%

484 Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model

Lü

et al. 2017

Journal of Investigative Dermatology

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“…While skeletal muscle is one of the few tissues that can regenerate throughout life, it was thought that the presence of the existing extracellular matrix template of the injured muscle was an absolute requirement for regeneration. This has also been demonstrated to be true of panniculus carnosus as well, where after full‐thickness excisional wounding, the severed myofibres of the panniculus carnosus undergo repair by proliferation and differentiation of satellite cells, but no new myofibres regenerate in the wound area . However, in contrast to previous dogma, Acomys appears to be capable of de novo regeneration of the panniculus carnosus, in the absence of an existing ECM template.…”

Section: Skin Regeneration After Full‐thickness Excision or Burn Injurymentioning

confidence: 88%

“…This tissue, while largely vestigial in humans, is ubiquitous in mammals and allows for twitching movement of the skin as well as thermoregulation and is well developed in both M. musculus and Acomys (Figure A,B). The panniculus carnosus has a higher level of cell turnover during muscle homoeostasis, as well as a higher frequency of incorporation of bone marrow‐derived cells, compared to limb skeletal muscles . While skeletal muscle is one of the few tissues that can regenerate throughout life, it was thought that the presence of the existing extracellular matrix template of the injured muscle was an absolute requirement for regeneration.…”

Section: Skin Regeneration After Full‐thickness Excision or Burn Injurymentioning

confidence: 99%

“…The panniculus carnosus has a higher level of cell turnover during muscle homoeostasis, as well as a higher frequency of incorporation of bone marrow-derived cells, compared to limb skeletal muscles. [29] While skeletal muscle is one of the few tissues that can regenerate throughout life, it was thought that the presence of the existing extracellular matrix template of the injured muscle was an absolute requirement for regeneration. This has also been demonstrated to be true of panniculus carnosus as well, where after full-thickness excisional wounding, the severed myofibres of the panniculus carnosus undergo repair by proliferation and differentiation of satellite cells, but no new myofibres regenerate in the wound area.…”

Section: Response Of the Panniculus Carnosusmentioning

confidence: 99%

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Insights into the regeneration of skin from Acomys, the spiny mouse

Maden

Brant

2019

Experimental Dermatology

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Members of the Acomys genus, known as spiny mice, are unique among mammals in being perfectly capable of regenerating large areas of skin that have been removed. During this regenerative process hairs, sebaceous glands, erector pili muscles, adipocytes and the panniculus carnosus all regenerate and the dermis does not scar. We review here the processes that the epidermis and the individual components of the dermis undergo during spiny mouse regeneration as well as the molecules that have been identified as potentially important in regeneration. We then relate this to what has been proposed as playing a role in studies from the laboratory mouse, Mus musculus. Differences in the immune systems of spiny mice and laboratory mice are also highlighted as this is suggested to play a part not only in the perfect wound healing that embryos display but also in regeneration in lower vertebrates.

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“…6 However, Pax7 expressing cells in wound repair 6 may in fact be SCs from the dermal panniculus carnosus muscle present in the rodents' skin. 7 This interesting study opens several questions. Quantitative comparison of Pax7 expression in MEFs with the level observed in differentiating ESCs would be informative.…”

mentioning

confidence: 98%

Many roles for Pax7

Dulak

2016

Cell Cycle

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Identification and Characterization of the Dermal Panniculus Carnosus Muscle Stem Cells

Cited by 34 publications

References 60 publications

484 Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model

484 Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model

Insights into the regeneration of skin from Acomys, the spiny mouse

Many roles for Pax7

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