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Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors

Bar-Nur, O; Gerli, MFM; Di Stefano, B; Almada, AE; Galvin, A; Coffey, A; Huebner, AJ; ... Hochedlinger, K; + view all (2018) Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors. Stem Cell Reports , 10 (5) pp. 1505-1521. 10.1016/j.stemcr.2018.04.009. Green open access

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Abstract

Skeletal muscle harbors quiescent stem cells termed satellite cells and proliferative progenitors termed myoblasts, which play pivotal roles during muscle regeneration. However, current technology does not allow permanent capture of these cell populations in vitro. Here, we show that ectopic expression of the myogenic transcription factor MyoD, combined with exposure to small molecules, reprograms mouse fibroblasts into expandable induced myogenic progenitor cells (iMPCs). iMPCs express key skeletal muscle stem and progenitor cell markers including Pax7 and Myf5 and give rise to dystrophin-expressing myofibers upon transplantation in vivo. Notably, a subset of transplanted iMPCs maintain Pax7 expression and sustain serial regenerative responses. Similar to satellite cells, iMPCs originate from Pax7+ cells and require Pax7 itself for maintenance. Finally, we show that myogenic progenitor cell lines can be established from muscle tissue following small-molecule exposure alone. This study thus reports on a robust approach to derive expandable myogenic stem/progenitor-like cells from multiple cell types.

Type: Article
Title: Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.stemcr.2018.04.009
Publisher version: https://doi.org/10.1016/j.stemcr.2018.04.009
Language: English
Additional information: Copyright © 2018 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creative commons.org/licenses/by-nc-nd/4.0/)
Keywords: skeletal muscle, satellite cells, direct lineage reprogramming, induced muscle progenitor cells, MyoD, Pax7, small molecules, transplantation, muscular dystrophy
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/10049638
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