Metabolic Changes During In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2024 Jan 11

PMID 38201280

Authors

Phablo Abreu

Bayardo I Garay

Travis Nemkov

Aline M S Yamashita

Rita C R Perlingeiro

Affiliations

Soon will be listed here.

Abstract

In vitro-generated pluripotent stem cell (PSC)-derived Pax3-induced (iPax3) myogenic progenitors display an embryonic transcriptional signature, but upon engraftment, the profile of re-isolated iPax3 donor-derived satellite cells changes toward similarity with postnatal satellite cells, suggesting that engrafted PSC-derived myogenic cells remodel their transcriptional signature upon interaction within the adult muscle environment. Here, we show that engrafted myogenic progenitors also remodel their metabolic state. Assessment of oxygen consumption revealed that exposure to the adult muscle environment promotes overt changes in mitochondrial bioenergetics, as shown by the substantial suppression of energy requirements in re-isolated iPax3 donor-derived satellite cells compared to their in vitro-generated progenitors. Mass spectrometry-based metabolomic profiling further confirmed the relationship of engrafted iPax3 donor-derived cells to adult satellite cells. The fact that in vitro-generated myogenic progenitors remodel their bioenergetic signature upon in vivo exposure to the adult muscle environment may have important implications for therapeutic applications.

Citing Articles

Effect of Notch1 signaling on muscle engraftment and maturation from pluripotent stem cells.

Yamashita A, Garay B, Kim H, Bosnakovski D, Abrahante J, Azzag K Stem Cell Reports. 2025; 20(2):102396.

PMID: 39889709 PMC: 11864150. DOI: 10.1016/j.stemcr.2024.102396.

Metabolic regulation in adult and aging skeletal muscle stem cells.

Sartorelli V, Ciuffoli V Genes Dev. 2024; 39(3-4):186-208.

PMID: 39662967 PMC: 11789647. DOI: 10.1101/gad.352277.124.

Alcohol Impairs Bioenergetics and Differentiation Capacity of Myoblasts from Simian Immunodeficiency Virus-Infected Female Macaques.

Levitt D, Bourgeois B, Rodriguez-Graciani K, Molina P, Simon L Int J Mol Sci. 2024; 25(4).

PMID: 38397125 PMC: 10888832. DOI: 10.3390/ijms25042448.

References

Filareto A, Darabi R, Perlingeiro R . Engraftment of ES-Derived Myogenic Progenitors in a Severe Mouse Model of Muscular Dystrophy. J Stem Cell Res Ther. 2013; 10(1). PMC: 3593119. DOI: 10.4172/2157-7633.S10-001. View

Darabi R, Gehlbach K, Bachoo R, Kamath S, Osawa M, Kamm K . Functional skeletal muscle regeneration from differentiating embryonic stem cells. Nat Med. 2008; 14(2):134-43. DOI: 10.1038/nm1705. View

Kirkeby A, Nelander J, Hoban D, Rogelius N, Bjartmarz H, Storm P . Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD. Cell Stem Cell. 2023; 30(10):1299-1314.e9. DOI: 10.1016/j.stem.2023.08.014. View

Kim D, Paggi J, Park C, Bennett C, Salzberg S . Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat Biotechnol. 2019; 37(8):907-915. PMC: 7605509. DOI: 10.1038/s41587-019-0201-4. View

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

Darabi R, Santos F, Filareto A, Pan W, Koene R, Rudnicki M . Assessment of the myogenic stem cell compartment following transplantation of Pax3/Pax7-induced embryonic stem cell-derived progenitors. Stem Cells. 2011; 29(5):777-90. PMC: 3325545. DOI: 10.1002/stem.625. View

Pang Z, Zhou G, Ewald J, Chang L, Hacariz O, Basu N . Using MetaboAnalyst 5.0 for LC-HRMS spectra processing, multi-omics integration and covariate adjustment of global metabolomics data. Nat Protoc. 2022; 17(8):1735-1761. DOI: 10.1038/s41596-022-00710-w. View

Beauchamp J, Heslop L, Yu D, Tajbakhsh S, Kelly R, Wernig A . Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. J Cell Biol. 2000; 151(6):1221-34. PMC: 2190588. DOI: 10.1083/jcb.151.6.1221. View

Ma H, Wert K, Shvartsman D, Melton D, Jaenisch R . Establishment of human pluripotent stem cell-derived pancreatic β-like cells in the mouse pancreas. Proc Natl Acad Sci U S A. 2018; 115(15):3924-3929. PMC: 5899428. DOI: 10.1073/pnas.1702059115. View

10.

Yucel N, Wang Y, Mai T, Porpiglia E, Lund P, Markov G . Glucose Metabolism Drives Histone Acetylation Landscape Transitions that Dictate Muscle Stem Cell Function. Cell Rep. 2019; 27(13):3939-3955.e6. PMC: 6788807. DOI: 10.1016/j.celrep.2019.05.092. View

11.

Hogrebe N, Ishahak M, Millman J . Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes. Cell Stem Cell. 2023; 30(5):530-548. PMC: 10167558. DOI: 10.1016/j.stem.2023.04.002. View

12.

Mourikis P, Sambasivan R, Castel D, Rocheteau P, Bizzarro V, Tajbakhsh S . A critical requirement for notch signaling in maintenance of the quiescent skeletal muscle stem cell state. Stem Cells. 2011; 30(2):243-52. DOI: 10.1002/stem.775. View

13.

Olguin H, Olwin B . Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: a potential mechanism for self-renewal. Dev Biol. 2004; 275(2):375-88. PMC: 3322464. DOI: 10.1016/j.ydbio.2004.08.015. View

14.

Wen Y, Bi P, Liu W, Asakura A, Keller C, Kuang S . Constitutive Notch activation upregulates Pax7 and promotes the self-renewal of skeletal muscle satellite cells. Mol Cell Biol. 2012; 32(12):2300-11. PMC: 3372272. DOI: 10.1128/MCB.06753-11. View

15.

Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z . clusterProfiler 4.0: A universal enrichment tool for interpreting omics data. Innovation (Camb). 2021; 2(3):100141. PMC: 8454663. DOI: 10.1016/j.xinn.2021.100141. View

16.

Sun C, Kannan S, Choi I, Lim H, Zhang H, Chen G . Human pluripotent stem cell-derived myogenic progenitors undergo maturation to quiescent satellite cells upon engraftment. Cell Stem Cell. 2022; 29(4):610-619.e5. PMC: 9000524. DOI: 10.1016/j.stem.2022.03.004. View

17.

Hargus G, Cooper O, Deleidi M, Levy A, Lee K, Marlow E . Differentiated Parkinson patient-derived induced pluripotent stem cells grow in the adult rodent brain and reduce motor asymmetry in Parkinsonian rats. Proc Natl Acad Sci U S A. 2010; 107(36):15921-6. PMC: 2936617. DOI: 10.1073/pnas.1010209107. View

18.

Dhoke N, Kim H, Selvaraj S, Azzag K, Zhou H, Oliveira N . A universal gene correction approach for FKRP-associated dystroglycanopathies to enable autologous cell therapy. Cell Rep. 2021; 36(2):109360. PMC: 8327854. DOI: 10.1016/j.celrep.2021.109360. View

19.

Magli A, Incitti T, Kiley J, Swanson S, Darabi R, Rinaldi F . PAX7 Targets, CD54, Integrin α9β1, and SDC2, Allow Isolation of Human ESC/iPSC-Derived Myogenic Progenitors. Cell Rep. 2017; 19(13):2867-2877. PMC: 5528177. DOI: 10.1016/j.celrep.2017.06.005. View

20.

Montarras D, Morgan J, Collins C, Relaix F, Zaffran S, Cumano A . Direct isolation of satellite cells for skeletal muscle regeneration. Science. 2005; 309(5743):2064-7. DOI: 10.1126/science.1114758. View