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Epithelial–mesenchymal transition: an organizing principle of mammalian regeneration

Introduction: The MRL mouse strain is one of the few examples of a mammal capable of healing appendage wounds by regeneration, a process that begins with the formation of a blastema, a structure containing de-differentiating mesenchymal cells. HIF-1α expression in the nascent MRL wound site blastema...

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Autores principales: Bedelbaeva, Kamila, Cameron, Benjamin, Latella, John, Aslanukov, Azamat, Gourevitch, Dmitri, Davuluri, Ramana, Heber-Katz, Ellen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641390/
https://www.ncbi.nlm.nih.gov/pubmed/37965571
http://dx.doi.org/10.3389/fcell.2023.1101480
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author Bedelbaeva, Kamila
Cameron, Benjamin
Latella, John
Aslanukov, Azamat
Gourevitch, Dmitri
Davuluri, Ramana
Heber-Katz, Ellen
author_facet Bedelbaeva, Kamila
Cameron, Benjamin
Latella, John
Aslanukov, Azamat
Gourevitch, Dmitri
Davuluri, Ramana
Heber-Katz, Ellen
author_sort Bedelbaeva, Kamila
collection PubMed
description Introduction: The MRL mouse strain is one of the few examples of a mammal capable of healing appendage wounds by regeneration, a process that begins with the formation of a blastema, a structure containing de-differentiating mesenchymal cells. HIF-1α expression in the nascent MRL wound site blastema is one of the earliest identified events and is sufficient to initiate the complete regenerative program. However, HIF-1α regulates many cellular processes modulating the expression of hundreds of genes. A later signal event is the absence of a functional G1 checkpoint, leading to G2 cell cycle arrest with increased cellular DNA but little cell division observed in the blastema. This lack of mitosis in MRL blastema cells is also a hallmark of regeneration in classical invertebrate and vertebrate regenerators such as planaria, hydra, and newt. Results and discussion: Here, we explore the cellular events occurring between HIF-1α upregulation and its regulation of the genes involved in G2 arrest (EVI-5, γH3, Wnt5a, and ROR2), and identify epithelial–mesenchymal transition (EMT) (Twist and Slug) and chromatin remodeling (EZH-2 and H3K27me3) as key intermediary processes. The locus of these cellular events is highly regionalized within the blastema, occurring in the same cells as determined by double staining by immunohistochemistry and FACS analysis, and appears as EMT and chromatin remodeling, followed by G2 arrest determined by kinetic expression studies.
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spelling pubmed-106413902023-11-14 Epithelial–mesenchymal transition: an organizing principle of mammalian regeneration Bedelbaeva, Kamila Cameron, Benjamin Latella, John Aslanukov, Azamat Gourevitch, Dmitri Davuluri, Ramana Heber-Katz, Ellen Front Cell Dev Biol Cell and Developmental Biology Introduction: The MRL mouse strain is one of the few examples of a mammal capable of healing appendage wounds by regeneration, a process that begins with the formation of a blastema, a structure containing de-differentiating mesenchymal cells. HIF-1α expression in the nascent MRL wound site blastema is one of the earliest identified events and is sufficient to initiate the complete regenerative program. However, HIF-1α regulates many cellular processes modulating the expression of hundreds of genes. A later signal event is the absence of a functional G1 checkpoint, leading to G2 cell cycle arrest with increased cellular DNA but little cell division observed in the blastema. This lack of mitosis in MRL blastema cells is also a hallmark of regeneration in classical invertebrate and vertebrate regenerators such as planaria, hydra, and newt. Results and discussion: Here, we explore the cellular events occurring between HIF-1α upregulation and its regulation of the genes involved in G2 arrest (EVI-5, γH3, Wnt5a, and ROR2), and identify epithelial–mesenchymal transition (EMT) (Twist and Slug) and chromatin remodeling (EZH-2 and H3K27me3) as key intermediary processes. The locus of these cellular events is highly regionalized within the blastema, occurring in the same cells as determined by double staining by immunohistochemistry and FACS analysis, and appears as EMT and chromatin remodeling, followed by G2 arrest determined by kinetic expression studies. Frontiers Media S.A. 2023-10-26 /pmc/articles/PMC10641390/ /pubmed/37965571 http://dx.doi.org/10.3389/fcell.2023.1101480 Text en Copyright © 2023 Bedelbaeva, Cameron, Latella, Aslanukov, Gourevitch, Davuluri and Heber-Katz. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Bedelbaeva, Kamila
Cameron, Benjamin
Latella, John
Aslanukov, Azamat
Gourevitch, Dmitri
Davuluri, Ramana
Heber-Katz, Ellen
Epithelial–mesenchymal transition: an organizing principle of mammalian regeneration
title Epithelial–mesenchymal transition: an organizing principle of mammalian regeneration
title_full Epithelial–mesenchymal transition: an organizing principle of mammalian regeneration
title_fullStr Epithelial–mesenchymal transition: an organizing principle of mammalian regeneration
title_full_unstemmed Epithelial–mesenchymal transition: an organizing principle of mammalian regeneration
title_short Epithelial–mesenchymal transition: an organizing principle of mammalian regeneration
title_sort epithelial–mesenchymal transition: an organizing principle of mammalian regeneration
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10641390/
https://www.ncbi.nlm.nih.gov/pubmed/37965571
http://dx.doi.org/10.3389/fcell.2023.1101480
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