scholarly journals Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA lnc-Rewind in muscle stem cells

2020 ◽  
Author(s):  
Andrea Cipriano ◽  
Martina Macino ◽  
Giulia Buonaiuto ◽  
Tiziana Santini ◽  
Beatrice Biferali ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Epigenetic Regulation ◽  
Noncoding Rna ◽  
Muscle Stem Cells ◽  
Cis Acting ◽  
Adult Muscle ◽  
Histone Lysine Methyltransferase ◽  
Muscle Genes ◽  
Muscle Homeostasis

ABSTRACTSkeletal muscle possesses an outstanding capacity to regenerate upon injury due to the adult muscle stem cells (MuSCs) activity. This ability requires the proper balance between MuSCs expansion and differentiation which is critical for muscle homeostasis and contributes, if deregulated, to muscle diseases. Here, we functionally characterize a novel chromatin-associated lncRNA, lnc-Rewind, which is expressed in murine MuSCs and conserved in human. We find that, in mouse, lnc-Rewind acts as an epigenetic regulator of MuSCs proliferation and expansion by influencing the expression of skeletal muscle genes and several components of the WNT (Wingless-INT) signalling pathway. Among them, we identified the nearby Wnt7b gene as a direct lnc-Rewind target. We show that lnc-Rewind interacts with the G9a histone lysine methyltransferase and mediates the in cis repression of Wnt7b by H3K9me2 deposition. Overall, these findings provide novel insights into the epigenetic regulation of adult muscle stem cells fate by lncRNAs.

scholarly journals Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA Lnc-Rewind in muscle stem cells

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Andrea Cipriano ◽  
Martina Macino ◽  
Giulia Buonaiuto ◽  
Tiziana Santini ◽  
Beatrice Biferali ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Epigenetic Regulation ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Muscle Stem Cells ◽  
Cis Acting ◽  
Adult Muscle ◽  
Histone Lysine Methyltransferase ◽  
Muscle Genes

Skeletal muscle possesses an outstanding capacity to regenerate upon injury due to the adult muscle stem cell (MuSC) activity. This ability requires the proper balance between MuSC expansion and differentiation, which is critical for muscle homeostasis and contributes, if deregulated, to muscle diseases. Here, we functionally characterize a novel chromatin-associated long noncoding RNA (lncRNA), Lnc-Rewind, which is expressed in murine MuSCs and conserved in human. We find that, in mouse, Lnc-Rewind acts as an epigenetic regulator of MuSC proliferation and expansion by influencing the expression of skeletal muscle genes and several components of the WNT (Wingless-INT) signalling pathway. Among them, we identified the nearby Wnt7b gene as a direct Lnc-Rewind target. We show that Lnc-Rewind interacts with the G9a histone lysine methyltransferase and mediates the in cis repression of Wnt7b by H3K9me2 deposition. Overall, these findings provide novel insights into the epigenetic regulation of adult muscle stem cells fate by lncRNAs.

scholarly journals APC is required for muscle stem cell proliferation and skeletal muscle tissue repair

2015 ◽  
Vol 210 (5) ◽  
pp. 717-726 ◽  
Author(s):  
Alice Parisi ◽  
Floriane Lacour ◽  
Lorenzo Giordani ◽  
Sabine Colnot ◽  
Pascal Maire ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Cycle Progression ◽  
Cell Types ◽  
Double Knockout ◽  
Muscle Stem Cells ◽  
Adult Muscle ◽  
Canonical Wnt

The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues.

scholarly journals Fibro-adipogenic progenitors in skeletal muscle homeostasis, regeneration and diseases

Open Biology ◽  
2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Thomas Molina ◽  
Paul Fabre ◽  
Nicolas A. Dumont
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscle Regeneration ◽  
New Technologies ◽  
Cell Activity ◽  
Cellular Heterogeneity ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury ◽  
Muscle Stem Cells ◽  
Muscle Homeostasis

Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of non-myogenic cells also plays a key role in the coordination of skeletal muscle regeneration. Particularly, fibro-adipogenic progenitors (FAPs) emerged as master regulators of muscle stem cell function and skeletal muscle regeneration. This population of muscle resident mesenchymal stromal cells has been initially characterized based on its bi-potent ability to differentiate into fibroblasts or adipocytes. New technologies such as single-cell RNAseq revealed the cellular heterogeneity of FAPs and their complex regulatory network during muscle regeneration. In acute injury, FAPs rapidly enter the cell cycle and secrete trophic factors that support the myogenic activity of muscle stem cells. Conversely, deregulation of FAP cell activity is associated with the accumulation of fibrofatty tissue in pathological conditions such as muscular dystrophies and ageing. Considering their central role in skeletal muscle pathophysiology, the regulatory mechanisms of FAPs and their cellular and molecular crosstalk with muscle stem cells are highly investigated in the field. In this review, we summarize the current knowledge on FAP cell characteristics, heterogeneity and the cellular crosstalk during skeletal muscle homeostasis and regeneration. We further describe their role in muscular disorders, as well as different therapeutic strategies targeting these cells to restore muscle regeneration.

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