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Partial reprogramming restores youthful gene expression through transient suppression of cell identity

Antoine Roux, Chunlian Zhang, Jonathan Paw, José Zavala-Solorio, Twaritha Vijay, Ganesh Kolumam, Cynthia Kenyon, View ORCID ProfileJacob C. Kimmel
doi: https://doi.org/10.1101/2021.05.21.444556
Antoine Roux
1Calico Life Sciences LLC,
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Chunlian Zhang
1Calico Life Sciences LLC,
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Jonathan Paw
1Calico Life Sciences LLC,
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José Zavala-Solorio
1Calico Life Sciences LLC,
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Twaritha Vijay
1Calico Life Sciences LLC,
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Ganesh Kolumam
1Calico Life Sciences LLC,
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Cynthia Kenyon
1Calico Life Sciences LLC,
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Jacob C. Kimmel
1Calico Life Sciences LLC,
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  • For correspondence: jacobkimmel@gmail.com jacob@calicolabs.com
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Abstract

Transient induction of pluripotent reprogramming factors has been reported to reverse some features of aging in mammalian cells and tissues. However, the impact of transient reprogramming on somatic cell identity programs and the necessity of individual pluripotency factors remain unknown. Here, we mapped trajectories of transient reprogramming in young and aged cells from multiple murine cell types using single cell transcriptomics to address these questions. We found that transient reprogramming restored youthful gene expression in adipogenic cells and mesenchymal stem cells but also temporarily suppressed somatic cell identity programs. We further screened Yamanaka Factor subsets and found that many combinations had an impact on aging gene expression and suppressed somatic identity, but that these effects were not tightly entangled. We also found that a transient reprogramming approach inspired by amphibian regeneration restored youthful gene expression in aged myogenic cells. Our results suggest that transient pluripotent reprogramming poses a neoplastic risk, but that restoration of youthful gene expression can be achieved with alternative strategies.

Competing Interest Statement

All authors are paid employees of Calico Life Sciences LLC, South San Francisco, California, 94080.

Footnotes

  • https://reprog.research.calicolabs.com

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 23, 2021.
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Partial reprogramming restores youthful gene expression through transient suppression of cell identity
Antoine Roux, Chunlian Zhang, Jonathan Paw, José Zavala-Solorio, Twaritha Vijay, Ganesh Kolumam, Cynthia Kenyon, Jacob C. Kimmel
bioRxiv 2021.05.21.444556; doi: https://doi.org/10.1101/2021.05.21.444556
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Partial reprogramming restores youthful gene expression through transient suppression of cell identity
Antoine Roux, Chunlian Zhang, Jonathan Paw, José Zavala-Solorio, Twaritha Vijay, Ganesh Kolumam, Cynthia Kenyon, Jacob C. Kimmel
bioRxiv 2021.05.21.444556; doi: https://doi.org/10.1101/2021.05.21.444556

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