Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming
The axolotl (Ambystoma mexicanum) is a caudate amphibian, which has an extraordinary ability to restore a wide variety of damaged structures by a process denominated epimorphosis. While the origin and potentiality of progenitor cells that take part during epimorphic regeneration are known to some ex...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.562940/full |
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| author | Hugo Varela-Rodríguez Diana G. Abella-Quintana Annie Espinal-Centeno Luis Varela-Rodríguez David Gomez-Zepeda Juan Caballero-Pérez Paola L. García-Medel Luis G. Brieba José J. Ordaz-Ortiz Alfredo Cruz-Ramirez |
| author_facet | Hugo Varela-Rodríguez Diana G. Abella-Quintana Annie Espinal-Centeno Luis Varela-Rodríguez David Gomez-Zepeda Juan Caballero-Pérez Paola L. García-Medel Luis G. Brieba José J. Ordaz-Ortiz Alfredo Cruz-Ramirez |
| author_sort | Hugo Varela-Rodríguez |
| collection | DOAJ |
| description | The axolotl (Ambystoma mexicanum) is a caudate amphibian, which has an extraordinary ability to restore a wide variety of damaged structures by a process denominated epimorphosis. While the origin and potentiality of progenitor cells that take part during epimorphic regeneration are known to some extent, the metabolic changes experienced and their associated implications, remain unexplored. However, a circuit with a potential role as a modulator of cellular metabolism along regeneration is that formed by Lin28/let-7. In this study, we report two Lin28 paralogs and eight mature let-7 microRNAs encoded in the axolotl genome. Particularly, in the proliferative blastema stage amxLin28B is more abundant in the nuclei of blastemal cells, while the microRNAs amx-let-7c and amx-let-7a are most downregulated. Functional inhibition of Lin28 factors increase the levels of most mature let-7 microRNAs, consistent with an increment of intermediary metabolites of the Krebs cycle, and phenotypic alterations in the outgrowth of the blastema. In summary, we describe the primary components of the Lin28/let-7 circuit and their function during axolotl regeneration, acting upstream of metabolic reprogramming events. |
| first_indexed | 2024-12-12T17:16:26Z |
| format | Article |
| id | doaj.art-cf9b38cf898e4836ab2caea4a387f79b |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-12T17:16:26Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-cf9b38cf898e4836ab2caea4a387f79b2022-12-22T00:17:47ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-11-01810.3389/fcell.2020.562940562940Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic ReprogrammingHugo Varela-Rodríguez0Diana G. Abella-Quintana1Annie Espinal-Centeno2Luis Varela-Rodríguez3David Gomez-Zepeda4Juan Caballero-Pérez5Paola L. García-Medel6Luis G. Brieba7José J. Ordaz-Ortiz8Alfredo Cruz-Ramirez9Molecular and Developmental Complexity Group, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, MexicoMolecular and Developmental Complexity Group, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, MexicoMolecular and Developmental Complexity Group, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, MexicoFacultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Chihuahua, MexicoMass Spectrometry and Metabolomics Laboratory, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, MexicoMolecular and Developmental Complexity Group, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, MexicoStructural Biochemistry Group, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, MexicoStructural Biochemistry Group, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, MexicoMass Spectrometry and Metabolomics Laboratory, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, MexicoMolecular and Developmental Complexity Group, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, MexicoThe axolotl (Ambystoma mexicanum) is a caudate amphibian, which has an extraordinary ability to restore a wide variety of damaged structures by a process denominated epimorphosis. While the origin and potentiality of progenitor cells that take part during epimorphic regeneration are known to some extent, the metabolic changes experienced and their associated implications, remain unexplored. However, a circuit with a potential role as a modulator of cellular metabolism along regeneration is that formed by Lin28/let-7. In this study, we report two Lin28 paralogs and eight mature let-7 microRNAs encoded in the axolotl genome. Particularly, in the proliferative blastema stage amxLin28B is more abundant in the nuclei of blastemal cells, while the microRNAs amx-let-7c and amx-let-7a are most downregulated. Functional inhibition of Lin28 factors increase the levels of most mature let-7 microRNAs, consistent with an increment of intermediary metabolites of the Krebs cycle, and phenotypic alterations in the outgrowth of the blastema. In summary, we describe the primary components of the Lin28/let-7 circuit and their function during axolotl regeneration, acting upstream of metabolic reprogramming events.https://www.frontiersin.org/articles/10.3389/fcell.2020.562940/fullLin28let-7epimorphic regenerationaxolotl (Ambystoma mexicanum)metabolic reprogramming |
| spellingShingle | Hugo Varela-Rodríguez Diana G. Abella-Quintana Annie Espinal-Centeno Luis Varela-Rodríguez David Gomez-Zepeda Juan Caballero-Pérez Paola L. García-Medel Luis G. Brieba José J. Ordaz-Ortiz Alfredo Cruz-Ramirez Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming Frontiers in Cell and Developmental Biology Lin28 let-7 epimorphic regeneration axolotl (Ambystoma mexicanum) metabolic reprogramming |
| title | Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming |
| title_full | Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming |
| title_fullStr | Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming |
| title_full_unstemmed | Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming |
| title_short | Functional Characterization of the Lin28/let-7 Circuit During Forelimb Regeneration in Ambystoma mexicanum and Its Influence on Metabolic Reprogramming |
| title_sort | functional characterization of the lin28 let 7 circuit during forelimb regeneration in ambystoma mexicanum and its influence on metabolic reprogramming |
| topic | Lin28 let-7 epimorphic regeneration axolotl (Ambystoma mexicanum) metabolic reprogramming |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.562940/full |
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