Identification of a Myogenic and Highly Transplantable Tert Expressing Non-Satellite Stem Cell Population

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Abstract/Contents

Abstract
Telomerase Reverse Transcriptase (Tert), a component of the telomerase holoenzyme complex, has been previously identified as a marker of stem cell populations across tissues. However, its role in skeletal muscle is poorly understood. In skeletal muscle, volumetric muscle loss injuries pose a unique challenge for cellular-based therapies, which so far have been relatively unsuccessful in preclinical models. Using a Tert-lineage tracing genetic mouse model, we identified a set of rare Tert expressing cells distributed throughout muscle. These Tert-lineage cells expand upon injury and contribute to myofiber regeneration in a delayed fashion. In addition, muscular regeneration upon repeated injuries is impaired by the loss of Tert in Tert expressing cells and their progeny. While a very small population of satellite cells express Tert, we also identified a population of Tert Expressing Multipotent Myogenic Progenitors (TEMMPros). These TEMMPros are multipotent and myogenic in vitro and via transplantation in a Tert-dependent manner. Furthermore, transplantation of these TEMMPros resulted in improved regeneration compared to satellite cells in a mouse model of volumetric muscle loss. Single-cell sequencing reveals that TEMMPros are transcriptionally distinct from other known skeletal muscle cell populations including satellite cells. These observations identify a novel subset of myogenic, non-satellite Tert expressing cells in mice that possess remarkable capacity for regeneration and may serve as a cell-based therapeutic for skeletal muscle damage.

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Type of resource text
Date modified December 5, 2022
Publication date May 5, 2022; May 2022

Creators/Contributors

Author Kim, Stewart
Thesis advisor Artandi, Steven
Thesis advisor Morrison, Ashby
Thesis advisor Mudgett, Mary Beth
Degree granting institution Stanford University, Department of Biology

Subjects

Subject Biology
Subject Skeletal Muscle
Subject Stem Cells
Subject Telomerase
Subject Regenerative Medicine
Genre Text
Genre Thesis

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Preferred citation
Kim, S. and Artandi, S. (2023). Identification of a Myogenic and Highly Transplantable Tert Expressing Non-Satellite Stem Cell Population. Stanford Digital Repository. Available at https://purl.stanford.edu/ys097rr2365

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Undergraduate Theses, Department of Biology, 2021-2022

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