ApoE isoform does not influence skeletal muscle regeneration in adult mice

B. I. Burke, J. Goh, F. A. Albathi, T. R. Valentino, G. L. Nolt, J. K. Joshi, C. M. Dungan, L. A. Johnson, Y. Wen, A. Ismaeel, J. J. McCarthy

Research output: Contribution to journalArticlepeer-review


Introduction: Apolipoprotein E (ApoE) has been shown to be necessary for proper skeletal muscle regeneration. Consistent with this finding, single-cell RNA-sequencing analyses of skeletal muscle stem cells (MuSCs) revealed that Apoe is a top marker of quiescent MuSCs that is downregulated upon activation. The purpose of this study was to determine if muscle regeneration is altered in mice which harbor one of the three common human ApoE isoforms, referred to as ApoE2, E3 and E4. Methods: Histomorphometric analyses were employed to assess muscle regeneration in ApoE2, E3, and E4 mice after 14 days of recovery from barium chloride-induced muscle damage in vivo, and primary MuSCs were isolated to assess proliferation and differentiation of ApoE2, E3, and E4 MuSCs in vitro. Results: There was no difference in the basal skeletal muscle phenotype of ApoE isoforms as evaluated by section area, myofiber cross-sectional area (CSA), and myonuclear and MuSC abundance per fiber. Although there were no differences in fiber-type frequency in the soleus, Type IIa relative frequency was significantly lower in plantaris muscles of ApoE4 mice compared to ApoE3. Moreover, ApoE isoform did not influence muscle regeneration as assessed by fiber frequency, fiber CSA, and myonuclear and MuSC abundance. Finally, there were no differences in the proliferative capacity or myogenic differentiation potential of MuSCs between any ApoE isoform. Discussion: Collectively, these data indicate nominal effects of ApoE isoform on the ability of skeletal muscle to regenerate following injury or the in vitro MuSC phenotype.
Original languageAmerican English
JournalFrontiers in Physiology
StatePublished - 2023

Bibliographical note

Burke, Benjamin I Goh, Jensen Albathi, Fatmah A Valentino, Taylor R Nolt, Georgia L Joshi, Jai K Dungan, Cory M Johnson, Lance A Wen, Yuan Ismaeel, Ahmed McCarthy, John J eng R01 AG060056/AG/NIA NIH HHS/ R01 AG069909/AG/NIA NIH HHS/ R01 AG080589/AG/NIA NIH HHS/ R01 AG081421/AG/NIA NIH HHS/ Switzerland 2023/12/11 Front Physiol. 2023 Nov 22;14:1302695. doi: 10.3389/fphys.2023.1302695. eCollection 2023.


  • Apoe MuSCs differentiation metabolism myogenesis proliferation regeneration satellite cells


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