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

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...

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Veröffentlicht in:The Journal of cell biology 2015-08, Vol.210 (5), p.717-726
Hauptverfasser: Parisi, Alice, Lacour, Floriane, Giordani, Lorenzo, Colnot, Sabine, Maire, Pascal, Le Grand, Fabien
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container_issue 5
container_start_page 717
container_title The Journal of cell biology
container_volume 210
creator Parisi, Alice
Lacour, Floriane
Giordani, Lorenzo
Colnot, Sabine
Maire, Pascal
Le Grand, Fabien
description 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.
doi_str_mv 10.1083/jcb.201501053
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subjects Adenomatous Polyposis Coli Protein - genetics
Adenomatous Polyposis Coli Protein - physiology
Adult Stem Cells - cytology
Adult Stem Cells - physiology
Animals
Apoptosis - genetics
beta Catenin - metabolism
Cell cycle
Cell Cycle - genetics
Cell Differentiation - genetics
Cell Differentiation - physiology
Cell Proliferation
Cell Survival - genetics
DNA repair
Female
Male
Mice
Mice, Transgenic
Muscle Development - genetics
Muscle Development - physiology
Muscle, Skeletal - cytology
Muscle, Skeletal - physiology
Musculoskeletal system
Regeneration - genetics
Regeneration - physiology
RNA Interference
RNA, Small Interfering - genetics
Satellite Cells, Skeletal Muscle - cytology
Satellite Cells, Skeletal Muscle - physiology
Signal transduction
Stem cells
Tissues
Wnt Proteins - metabolism
Wnt Signaling Pathway - genetics
Wound Healing - genetics
title APC is required for muscle stem cell proliferation and skeletal muscle tissue repair
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