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

Luis Varela-Rodríguez¹  David Gomez-Zepeda²  José J. Ordaz-Ortiz²  Alfredo Cruz-Ramirez³  Annie Espinal-Centeno³  Hugo Varela-Rodríguez³  Diana G. Abella-Quintana³  Juan Caballero-Pérez³  Paola L. García-Medel⁴  Luis G. Brieba⁴ 

[1] Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Chihuahua, Mexico;Mass Spectrometry and Metabolomics Laboratory, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, Mexico;Molecular and Developmental Complexity Group, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, Mexico;Structural Biochemistry Group, Unidad de Genómica Avanzada (LANGEBIO), Centro de Investigación y de Estudios Avanzados del IPN, Guanajuato, Mexico;

关键词: Lin28;    let-7;    epimorphic regeneration;    axolotl (Ambystoma mexicanum);    metabolic reprogramming;   

DOI  :  10.3389/fcell.2020.562940

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown