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Human cell dedifferentiation in mesenchymal condensates through controlled autophagy

Pennock, Rebecca; Bray, Elen; Pryor, Paul; James, Sally; McKeegan, Paul; Sturmey, Roger; Genever, Paul

Authors

Rebecca Pennock

Elen Bray

Paul Pryor

Sally James

Paul McKeegan

Paul Genever



Abstract

Tissue and whole organ regeneration is a dramatic biological response to injury that occurs across different plant and animal phyla. It frequently requires the dedifferentiation of mature cells to a condensed mesenchymal blastema, from which replacement tissues develop. Human somatic cells cannot regenerate in this way and differentiation is considered irreversible under normal developmental conditions. Here, we sought to establish in vitro conditions to mimic blastema formation by generating different three-dimensional (3D) condensates of human mesenchymal stromal cells (MSCs). We identified specific 3D growth environments that were sufficient to dedifferentiate aged human MSCs to an early mesendoderm-like state with reversal of age-associated cell hypertrophy and restoration of organized tissue regenerating capacity in vivo. An optimal auophagic response was required to promote cytoplasmic remodeling, mitochondrial regression, and a bioenergetic shift from oxidative phosphorylation to anaerobic metabolism. Our evidence suggests that human cell dedifferentiation can be achieved through autonomously controlled autophagic flux.

Publication Date 2015-10
Journal Scientific reports
Print ISSN 2045-2322
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 5
Issue 1
Article Number ARTN 13113
APA6 Citation Pennock, R., Bray, E., Pryor, P., James, S., McKeegan, P., Sturmey, R., & Genever, P. (2015). Human cell dedifferentiation in mesenchymal condensates through controlled autophagy. Scientific reports, 5(1), https://doi.org/10.1038/srep13113
DOI https://doi.org/10.1038/srep13113
Keywords Autophagy; Cell biology; Condensed mesenchymal blastema
Publisher URL http://www.nature.com/articles/srep13113
Copyright Statement This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Additional Information Copy of article first published in: Scientific reports, 2015, v.5.

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Copyright Statement
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/



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