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Molecular Strategies for Transdifferentiation of Retinal Pigment Epithelial Cells in Amphibians and Mammals In Vivo

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Abstract

Retinal pigment epithelium (RPE) is a source of cells for retinal regeneration in amphibians in vivo and the development of retinal diseases in mammals and humans. Transdifferentiation of RPE cells into cells of other phenotypes is the basis for both processes: RPE cells transform into neural in the first case and into mesenchymal cells in the second case. The review describes the main stages of RPE cell transdifferentiation: initiation of the process, cell migration and proliferation, dedifferentiation, reprogramming, and specialization of cells into new directions. Information about the molecular and genetic mechanisms that ensure the passage of these stages by cells is given. Molecular participants of the regulation of transdifferentiation on the levels of the whole organism, the local cellular microenvironment (growth factors, signaling cascades), the expression of transcription factors, and the epigenome regulation are presented. Similarities and differences in the molecular and genetic mechanisms of implementation of different strategies for RPE transdifferentiation in amphibians and mammals are noted. The discovery of key molecular regulators of this choice serves both for the development of the theory of cellular reprogramming and approaches for the treatment of proliferative diseases of the human retina associated with RPE pathologies.

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ACKNOWLEDGMENTS

The work was performed using the equipment of the Core Centrum of Koltsov Institute of Developmental Biology, Russian Academy Sciences.

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The work was performed within the framework of the State Assignment of Koltzov Institute of Developmental Biology of Russian Academy of Sciences, no. 0088-2021-0017.

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  1. Koltsov Institute of Developmental Biology, Russian Academy of Sciences, 119334, Moscow, Russia

    E. N. Grigoryan & Yu. V. Markitantova

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  1. E. N. Grigoryan
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The authors made an equal contribution to this study and to the preparation of the article.

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Correspondence to E. N. Grigoryan or Yu. V. Markitantova.

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Dedicated to the memory of our teachers, O.G. Stroeva and V.I. Mitashov

Translated by A. Ermakov

Abbreviations: RPE—retinal pigment epithelium; NR—neural retina; TF—transcription factor; EMT—epithelial-mesenchymal transition; EM– epiretinal membrane; PVR—proliferative vitreoretinopathy; ECM—extracellular matrix; PCR—polymerase chain reaction.

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Grigoryan, E.N., Markitantova, Y.V. Molecular Strategies for Transdifferentiation of Retinal Pigment Epithelial Cells in Amphibians and Mammals In Vivo. Russ J Dev Biol 52, 220–243 (2021). https://doi.org/10.1134/S1062360421040032

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  • DOI: https://doi.org/10.1134/S1062360421040032

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