m6A-mediated Cell-cell Communication Controls Planarian Regeneration

Cui, G.; Zhou, J.-Y.; Ge, X.-Y.; Sun, B.-F.; Song, G.-G.; Wang, X.; Wang, X.-Z.; Zhang, R.; Wang, H.; Jing, Q.; Zhao, Y.; Koziol, M.; Zeng, A.; Zhang, W.; Han, D.; Yang, Y.; Yang, Y.-G.

doi:10.1101/2021.07.29.454253

bioRxiv · 10.1101/2021.07.29.454253

m6A-mediated Cell-cell Communication Controls Planarian Regeneration

Cui, G.·Zhou, J.-Y.·Ge, X.-Y.·Sun, B.-F.·Song, G.-G.·Wang, X.·Wang, X.-Z.·Zhang, R.·Wang, H.·Jing, Q.·Zhao, Y.·Koziol, M.·Zeng, A.·Zhang, W.·Han, D.·Yang, Y.·Yang, Y.-G.

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Abstract

Regeneration is the regrowth of damaged tissues or organs, a vital mechanism responding to damages from primitive organisms to higher mammals. Planarian possesses active whole-body regenerative capability owning to its vast reservoir of adult stem cells, neoblasts, thus provides an ideal model to delineate the underlying mechanisms for regeneration. N6-methyladenosine (m6A) regulates stem cell renewal and differentiation. However, how m6A controls regeneration at whole-organism level remains largely unknown. Here, we demonstrate that the depletion of m6A methyltransferase regulatory subunit wtap abolishes planarian regeneration, through regulating cell-cell communication and cell cycle. scRNA-Seq analysis unveils that the wtap knockdown induces a unique type of neural progenitor-like cells (NP-like cells), characterized by specific expression of the cell-cell communication ligand grn. Intriguingly, the depletion of m6A-modified transcripts grn/cdk9 (or cdk7) axis rescues the defective regeneration of planarian without wtap. Overall, our study reveals an indispensable role of m6A-dependent cell-cell communication essential for whole-organism regeneration.

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Cui, G., Zhou, J.-Y., Ge, X.-Y., Sun, B.-F., Song, G.-G., Wang, X., Wang, X.-Z., Zhang, R., Wang, H., Jing, Q., Zhao, Y., Koziol, M., Zeng, A., Zhang, W., Han, D., Yang, Y., Yang, Y.-G.. 2021-07-29. m6A-mediated Cell-cell Communication Controls Planarian Regeneration. https://doi.org/10.1101/2021.07.29.454253

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